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1
Gladstone, R. A., J. M. Jefferies, S. N. Faust, and S. C. Clarke. "Continued control of pneumococcal disease in the UK – the impact of vaccination." Journal of Medical Microbiology 60, no. 1 (January 1, 2011): 1–8. http://dx.doi.org/10.1099/jmm.0.020016-0.
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Streptococcus pneumoniae, also known as the pneumococcus, is an important cause of morbidity and mortality in the developed and developing world. Pneumococcal conjugate vaccines were first introduced for routine use in the USA in 2000, although the seven-valent pneumococcal conjugate vaccine (PCV7) was not introduced into the UK's routine childhood immunization programme until September 2006. After its introduction, a marked decrease in the incidence of pneumococcal disease was observed, both in the vaccinated and unvaccinated UK populations. However, pneumococci are highly diverse and serotype prevalence is dynamic. Conversely, PCV7 targets only a limited number of capsular types, which appears to confer a limited lifespan to the observed beneficial effects. Shifts in serotype distribution have been detected for both non-invasive and invasive disease reported since PCV7 introduction, both in the UK and elsewhere. The pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix; GlaxoSmithKline) and 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar 13; Pfizer) have been newly licensed. The potential coverage of the 10- and 13-valent conjugate vaccines has also altered alongside serotype shifts. Nonetheless, the mechanism of how PCV7 has influenced serotype shift is not clear-cut as the epidemiology of serotype prevalence is complex. Other factors also influence prevalence and incidence of pneumococcal carriage and disease, such as pneumococcal diversity, levels of antibiotic use and the presence of risk groups. Continued surveillance and identification of factors influencing serotype distribution are essential to allow rational vaccine design, implementation and continued effective control of pneumococcal disease.
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van Tonder, Andries J., James E. Bray, Lucy Roalfe, Rebecca White, Marta Zancolli, Sigríður J. Quirk, Gunnsteinn Haraldsson, et al. "Genomics Reveals the Worldwide Distribution of Multidrug-Resistant Serotype 6E Pneumococci." Journal of Clinical Microbiology 53, no. 7 (May 13, 2015): 2271–85. http://dx.doi.org/10.1128/jcm.00744-15.
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The pneumococcus is a leading pathogen infecting children and adults. Safe, effective vaccines exist, and they work by inducing antibodies to the polysaccharide capsule (unique for each serotype) that surrounds the cell; however, current vaccines are limited by the fact that only a few of the nearly 100 antigenically distinct serotypes are included in the formulations. Within the serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and common colonizers of the nasopharynx in children. Serotype 6E was first reported in 2004 but was thought to be rare; however, we and others have detected serotype 6E among recent pneumococcal collections. Therefore, we analyzed a diverse data set of ∼1,000 serogroup 6 genomes, assessed the prevalence and distribution of serotype 6E, analyzed the genetic diversity among serogroup 6 pneumococci, and investigated whether pneumococcal conjugate vaccine-induced serotype 6A and 6B antibodies mediate the killing of serotype 6E pneumococci. We found that 43% of all genomes were of serotype 6E, and they were recovered worldwide from healthy children and patients of all ages with pneumococcal disease. Four genetic lineages, three of which were multidrug resistant, described ∼90% of the serotype 6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to elicit killing of serotype 6E pneumococci. We also revealed three major genetic clusters of serotype 6A capsular sequences, discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype switching. Therefore, while vaccines appear to offer protection against serotype 6E, genetic variants may reduce vaccine efficacy in the longer term because of the emergence of serotypes that can evade vaccine-induced immunity.
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Peter, Georges, and Jerome O. Klein. "Pneumococcal Vaccine." Pediatrics In Review 17, no. 10 (October 1, 1996): 335–41. http://dx.doi.org/10.1542/pir.17.10.335.
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Streptococcus pneumoniae, commonly termed the pneumococcus, is a major pediatric pathogen both in developed and developing countries. Despite the availability of multiple antimicrobials to which this organism is susceptible, it continues to cause significant morbidity and mortality. Recognition of the limitations of antimicrobial therapy in controlling the consequences of infection, particularly among high-risk persons such as those who have underlying pulmonary or cardiovascular disease and the elderly, led to the introduction in the 1970s of a polyvalent, polysaccharide pneumococcal vaccine. As a result, the current indications for vaccination of both children and adults are based on risk factors for severe, potentially life-threatening pneumococcal infections and, in the case of children, the age-related immunogenicity of the polysaccharide antigens of this vaccine. Appropriate use of this vaccine is facilitated by knowledge of the pathogenicity of S pneumoniae, epidemiology of the infections it causes, and the immunogenicity and efficacy of the vaccine. The limitations of the current pneumococcal vaccine not only affect management of vaccinated patients but also have prompted development of investigational vaccines for use among infants and young children. Polysaccharide-protein conjugate pneumococcal vaccines that have increased immunogenicity in infants are in clinical trials and will be discussed only briefly in this review.
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Sempere, Julio, Mirella Llamosí, Idoia del Río Menéndez, Beatriz López Ruiz, Mirian Domenech, and Fernando González-Camacho. "Pneumococcal Choline-Binding Proteins Involved in Virulence as Vaccine Candidates." Vaccines 9, no. 2 (February 20, 2021): 181. http://dx.doi.org/10.3390/vaccines9020181.
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Streptococcus pneumoniae is a pathogen responsible for millions of deaths worldwide. Currently, the available vaccines for the prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV-23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes (up to 100 different serotypes have been identified) and are unable to protect against non-vaccine serotypes and non-encapsulated pneumococci. The emergence of antibiotic-resistant non-vaccine serotypes after these vaccines is an increasing threat. Therefore, there is an urgent need to develop new pneumococcal vaccines which could cover a wide range of serotypes. One of the vaccines most characterized as a prophylactic alternative to current PPV-23 or PCVs is a vaccine based on pneumococcal protein antigens. The choline-binding proteins (CBP) are found in all pneumococcal strains, giving them the characteristic to be potential vaccine candidates as they may protect against different serotypes. In this review, we have focused the attention on different CBPs as vaccine candidates because they are involved in the pathogenesis process, confirming their immunogenicity and protection against pneumococcal infection. The review summarizes the major contribution of these proteins to virulence and reinforces the fact that antibodies elicited against many of them may block or interfere with their role in the infection process.
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Francois Watkins, Louise K., Jennifer L. Milucky, Lesley McGee,, Florence Siné St.-Surin, Pengbo Liu, Theresa Tran, Sopio Chochua, et al. "Nasopharyngeal Carriage of Streptococcus pneumoniae Among Young Children in Haiti Before Pneumococcal Conjugate Vaccine Introduction." Journal of Infectious Diseases 224, Supplement_3 (September 1, 2021): S248—S257. http://dx.doi.org/10.1093/infdis/jiab119.
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Abstract Background Streptococcus pneumoniae, or pneumococcus, is a leading cause of morbidity and mortality in children worldwide. Pneumococcal conjugate vaccines (PCV) reduce carriage in the nasopharynx, preventing disease. We conducted a pneumococcal carriage study to estimate the prevalence of pneumococcal colonization, identify risk factors for colonization, and describe antimicrobial susceptibility patterns among pneumococci colonizing young children in Port-au-Prince, Haiti, before introduction of 13-valent PCV (PCV13). Methods We conducted a cross-sectional study of children aged 6–24 months at an immunization clinic in Port-au-Prince between September 2015 and January 2016. Consenting parents were interviewed about factors associated with pneumococcal carriage; nasopharyngeal swabs were collected from each child and cultured for pneumococcus after broth enrichment. Pneumococcal isolates were serotyped and underwent antimicrobial susceptibility testing. We compared frequency of demographic, clinical, and environmental factors among pneumococcus-colonized children (carriers) to those who were not colonized (noncarriers) using unadjusted bivariate analysis and multivariate logistic regression. Results Pneumococcus was isolated from 308 of the 685 (45.0%) children enrolled. Overall, 157 isolates (50.8%) were PCV13 vaccine-type serotypes; most common were 6A (13.3%), 19F (12.6%), 6B (9.7%), and 23F (6.1%). Vaccine-type isolates were significantly more likely to be nonsusceptible to ≥1 antimicrobial (63.1% vs 45.4%, P = .002). On bivariate analysis, carriers were significantly more likely than noncarriers to live in a household without electricity or running water, to share a bedroom with ≥3 people, to have a mother or father who did not complete secondary education, and to have respiratory symptoms in the 24 hours before enrollment (P < .05 for all comparisons). On multivariable analysis, completion of the pentavalent vaccination series (targeting diphtheria, pertussis, tetanus, hepatitis B, and Haemophilus influenzae type b) remained significantly more common among noncarriers. Conclusions Nearly a quarter of healthy children surveyed in Haiti were colonized with vaccine-type pneumococcal serotypes. This baseline carriage study will enable estimation of vaccine impact following nationwide introduction of PCV13.
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Browall, Sarah, Erik Backhaus, Pontus Naucler, Ilias Galanis, Karin Sjöström, Diana Karlsson, Stefan Berg, et al. "Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types." European Respiratory Journal 44, no. 6 (October 16, 2014): 1646–57. http://dx.doi.org/10.1183/09031936.00080814.
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Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored.Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children.The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality.PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.
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PICHON, B., H. V. BENNETT, A. EFSTRATIOU, M. P. E. SLACK, and R. C. GEORGE. "Genetic characteristics of pneumococcal disease in elderly patients before introducing the pneumococcal conjugate vaccine." Epidemiology and Infection 137, no. 7 (January 23, 2009): 1049–56. http://dx.doi.org/10.1017/s0950268808001787.
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SUMMARYStreptococcus pneumoniaestrains causing invasive pneumococcal disease (IPD) in the elderly population of England and Wales during the winter of 2003/2004 (1 November 2003 to 30 April 2004) were characterized by serotyping and genotyping in order to determine their population structure in the elderly. Serotyping and multilocus sequence typing (MLST) were carried out on 542 invasive isolates referred to the Respiratory and Systemic Infection Laboratory. Pneumococci were distributed among 32 serotypes and 144 MLST sequence types. A high genetic diversity was observed within the major serotypes. Genetic relatedness varied with regard to serotype. Isolates within serotypes 3, 7F and 8 were the most genetically related whereas serotypes 6A and 19F comprised isolates originating from unrelated ancestors. There was indirect evidence that some pneumococci were derived from clones that had undergone capsular switching in the past. Interestingly one case of IPD was caused by a pneumococcus originating from a clone that had undergone capsular switching from serotype 18C, a serotype included in 7-valent pneumococcal conjugate vaccine (PCV) to serotype 1 (serotype not included in PCV) suggesting that virulent clones with the potential ability to evade PCV existed in the pneumococcal population prior to the routine introduction of this vaccine. Isolates from 28 cases of apparent 23-valent pneumococcal polysaccharide vaccine (PPV) failure were included but there was no evidence of the emergence of particular clones associated with vaccine failures. Longitudinal studies based on serotypic and genetic characterization of pneumococci are fundamental to understanding the impact of both PPV and PCV on the genetic structure of pneumococcal populations.
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Walekhwa, Michael, Fiona Maiyo, Teresa Kerubo, and Fred Kipsang. "In Vitro Evaluation of Effect of Storage Time on Immunogenicity of the 10-Valent Pneumococcal Conjugate Vaccine Using Baby Rabbit Complement & HL-60 Cells." Kabarak Journal of Research & Innovation 14, no. 01 (March 7, 2024): 16–25. http://dx.doi.org/10.58216/kjri.v14i01.280.
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Background: The efficacy and effectiveness of a vaccine is influenced by several factors including storage duration. Additionally, vaccines may be sufficiently administered but functionality of antibody generated may be hampered with by other factors such as nutritional status of the patient. As such, one of the ways of assessing vaccine efficacy is assessing the functionality of the antibodies generated. The 10v-PCV is a highly effective vaccine used to prevent invasive pneumococcal diseases in children. However, here in Kenya, cases of pneumococcal diseases are high and challenging to treat. This study thus aimed to evaluate the effect of storage of PCV-10 storage time on the functionality of Abs generated. Methodology; An in vitro experimental research design was employed for this study. opsonophagocytic activity assay using HL-60 Cells & Baby rabbit complement was used to assess whether or not the Pneumococci Serotype IgG antibodies elicited following administration with 10v-PCV vaccine are functional. Only 10v-PCV vaccine with same production date were procured. Twenty experimental rabbits of same gender were procured and used injected intraperitoneally with 3 doses of 100µl (0.34g) of 10v-PCV vaccine after every four weeks. Antibody functionality was then assessed using the opsonophagocytic activity assay method. Results: An average of 28.9% of pneumococcus exposed to the vaccine-induced secreted antibodies were killed by the pneumococcal IgG antibody. The highest percentage of number of bacteria killed was achieved after the 3rd dose of vaccination. There was no significant influence of storage duration on opsonophagocytic activity of generated antibodies. Conclusion: Storing of 10v-PCV vaccine up to 12 weeks does not significantly affect the opsonophagocytic activity of pneumococcal IgG antibodies.
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Ludwig, Endre, and Zsófia Mészner. "Prevention ofStreptococcus pneumoniae(pneumococcal) infections in adults." Orvosi Hetilap 155, no. 50 (December 2014): 1996–2004. http://dx.doi.org/10.1556/oh.2014.30070.
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Infections caused by Streptococcus pneumoniae (pneumococcus) are still meaning a serious health problem, about 40% of community acquired pneumonia (CAP) is due to pneumococcal bacteria in adults requiring hospitalization. The incidence and mortality rate of pneumococcal infections is increasing in the population above 50 years of age. Certain congenital and acquired immunocompromised conditions make the individual susceptible for pneumococcal infection and other chronic comorbidities should be considered as a risk factor as well, such as liver and renal diseases, COPD, diabetes mellitus. Lethality of severe pneumococcal infections with bacteraemia still remains about 12% despite adequate antimicrobial therapy in the past 60 years. Underestimation of pneumococcal infections is mainly due to the low sensitivity of diagnostic tools and underuse of bacteriological laboratory confirmation methods. 13-valent pneumococcal conjugate vaccine (PCV-13) became available recently beyond the 23-valent polysacharide vaccine (PPV-23) which has been using for a long time.The indication and proper administration of the two vaccines are based on international recommendations and vaccination guideline published by National Centre for Epidemiology (NCE):Pneumococcal vaccination is recommended for: Every person above 50 years of age. Patients of all ages with chronic diseases who are susceptible for severe pneumococcal infections: respiratory (COPD), heart, renal, liver disease, diabetes, or patients under immunsuppressive treatment. Smokers regardless of age and comorbidities. Cochlear implants, cranial-injured patients. Patients with asplenia.Recommendation for administration of the two different vaccines:Adults who have not been immunized previously against pneumococcal disease must be vaccinated with a dose of 13-valent pneumococcal conjugate vaccine first. This protection could be extended with administration of 23-valent pneumococcal polysaccharide vaccine at least two month later. Adults who have been immunized previously, but above 65 years of age, with a 23-valent polysaccharide vaccine are recommended to get one dose of conjugate vaccine at least one year later. Adults who have been immunized previously, but under 65 years of age, with a 23-valent polysaccharide vaccine are recommended to get one dose of conjugate vaccine at least one year later. After a minimal interval of two months one dose of 23-valent pneumococcal polysaccharide vaccine is recommended if at least 5 years have elapsed since their previous PPSV23 dose. Vaccination of immuncompromised patients (malignancy, transplantation, etc.) and patients with asplenia should be defined by vaccinology specialists. Pneumococcal vaccines may be administered concommitantly or any interval with other vaccines. Orv. Hetil., 2014, 155(50), 1996–2004.
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Baranov, Alexander A., Leyla S. Namazova-Baranova, Nikolay I. Brico, Yurii V. Lobzin, Roman S. Коzlov, Mikhail P. Kostinov, Irina S. Koroleva, et al. "Vaccine Prevention of Pneumococcal Infection in Children." Pediatric pharmacology 15, no. 3 (July 6, 2018): 200–211. http://dx.doi.org/10.15690/pf.v15i3.1899.
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Pneumococcal infection remains one of the leading reasons for infant mortality from vaccine-preventable infections. Today vaccination is the most effective way to prevent diseases caused by antibiotic-resistant pneumococci. In the article, authors present current approaches to vaccinal prevention of pneumococcal diseases. The plan of action for carrying out active immunoprophylaxis of pneumococcal infection is explained in detail for both healthy children and patients from risk groups for severe pneumococcal diseases development. The published work is based on key points of the guidelines of the Ministry of Health of the Russian Federation on vaccinal prevention of pneumococcal infection (developed and approved by the professional association of pediatricians «The Union of Pediatricians of Russia»).
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Morton, Ben, Kondwani Jambo, Tarsizio Chikaonda, Jamie Rylance, Marc Y. R. Henrion, Ndaziona Peter Banda, Edna Nsomba, Joel Gondwe, Daniela Ferreira, and Stephen B. Gordon. "The influence of pneumococcal conjugate vaccine-13 on nasal colonisation in a controlled human infection model of pneumococcal carriage in Malawi: a double-blinded randomised controlled trial protocol." Wellcome Open Research 6 (June 16, 2022): 240. http://dx.doi.org/10.12688/wellcomeopenres.17172.2.
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Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement, and demonstrate reduced effectiveness against mucosal colonisation. For Malawi, nasopharyngeal carriage of vaccine-type pneumococci is common in vaccinated children despite national roll-out of 13-valent pneumococcal conjugate vaccine (PCV13) since 2011. Our team has safely transferred an established experimental human pneumococcal carriage method from Liverpool School of Tropical Medicine to the Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi. This study will determine potential immunological mechanisms for the differential effects of PCV13 on nasal carriage between healthy Malawian and UK populations. We will conduct a double-blinded randomised controlled trial to vaccinate (1:1) participants with either PCV13 or control (normal saline). After a period of one month, participants will be inoculated with S. pneumoniae serotype 6B to experimentally induce nasal carriage using the EHPC method. Subsequently, participants will be invited for a second inoculation after one year to determine longer-term vaccine-induced immunological effects. Primary endpoint: detection of inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: local and systemic innate, humoral and cellular responses to PCV-13 with and without pneumococcal nasal carriage The primary objective of this controlled human infection model study is to determine if PCV-13 vaccination is protective against pneumococcal carriage in healthy adult Malawian volunteers. This study will help us to understand the observed differences in PCV-13 efficacy between populations and inform the design of future vaccines relevant to the Malawian population. Trial Registration: Pan African Clinical Trial Registry (REF: PACTR202008503507113)
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Morton, Ben, Kondwani Jambo, Tarsizio Chikaonda, Jamie Rylance, Marc Y. R. Henrion, Ndaziona Peter Banda, Edna Nsomba, Joel Gondwe, Daniela Ferreira, and Stephen B. Gordon. "The influence of pneumococcal conjugate vaccine-13 on nasal colonisation in a controlled human infection model of pneumococcal carriage in Malawi: a double-blinded randomised controlled trial protocol." Wellcome Open Research 6 (September 20, 2021): 240. http://dx.doi.org/10.12688/wellcomeopenres.17172.1.
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Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement, and demonstrate reduced effectiveness against mucosal colonisation. For Malawi, nasopharyngeal carriage of vaccine-type pneumococci is common in vaccinated children despite national roll-out of 13-valent pneumococcal conjugate vaccine (PCV13) since 2011. Our team has safely transferred an established experimental human pneumococcal carriage method from Liverpool School of Tropical Medicine to the Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi. This study will determine potential immunological mechanisms for the differential effects of PCV13 on nasal carriage between healthy Malawian and UK populations. We will conduct a double-blinded randomised controlled trial to vaccinate (1:1) participants with either PCV13 or control (normal saline). After a period of one month, participants will be inoculated with S. pneumoniae serotype 6B to experimentally induce nasal carriage using the EHPC method. Subsequently, participants will be invited for a second inoculation after one year to determine longer-term vaccine-induced immunological effects. Primary endpoint: detection of inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: local and systemic innate, humoral and cellular responses to PCV-13 with and without pneumococcal nasal carriage The primary objective of this controlled human infection model study is to determine if PCV-13 vaccination is protective against pneumococcal carriage in healthy adult Malawian volunteers. This study will help us to understand the observed differences in PCV-13 efficacy between populations and inform the design of future vaccines relevant to the Malawian population. Trial Registration: Pan African Clinical Trial Registry (REF: PACTR202008503507113)
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Salt, Penny, Carly Banner, Sarah Oh, Ly-mee Yu, Susan Lewis, Dingxin Pan, David Griffiths, Berne Ferry, and Andrew Pollard. "Social Mixing with Other Children during Infancy Enhances Antibody Response to a Pneumococcal Conjugate Vaccine in Early Childhood." Clinical and Vaccine Immunology 14, no. 5 (March 7, 2007): 593–99. http://dx.doi.org/10.1128/cvi.00344-06.
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ABSTRACT Children who have siblings and/or who attend day care have higher rates of nasopharyngeal colonization with pneumococci than lone children do. Pneumococcal colonization is usually asymptomatic but is a prerequisite for invasive disease. We studied the effect of social mixing with other children on immunity to a pneumococcal vaccine. One hundred sixty children aged 1 year were immunized with a 7-valent conjugate pneumococcal vaccine. A blood sample was obtained before and 9 to 11 days after the vaccine. The concentration and avidity of antibody against vaccine pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) were studied in relation to pneumococcal carriage rate and measures of social mixing. Children with increased social mixing had higher antibody concentrations against serotypes 4, 9V, 14, and 23F than lone children did. The least-carried serotype, serotype 4, was the one of the most immunogenic. This contrasts with serotype 6B, the most common nasopharyngeal isolate but the least immunogenic. Social mixing in infancy enhances the immune response to a Streptococcus pneumoniae polysaccharide-protein conjugate vaccine at 1 year of age. Exposure to pneumococci in the first year of life may induce immunological priming. An alternative explanation is that differences in immunological experience, such as increased exposure to respiratory viral infections in early childhood, alters the response to vaccines perhaps by affecting the balance between Th1 and Th2 cytokines. The low immunogenicity of serotype 6B polysaccharide might make conditions more favorable for carriage of the 6B organism and explain why 6B pneumococci were more frequently isolated than other serotypes.
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Jedrzejas, Mark J. "Pneumococcal Virulence Factors: Structure and Function." Microbiology and Molecular Biology Reviews 65, no. 2 (June 1, 2001): 187–207. http://dx.doi.org/10.1128/mmbr.65.2.187-207.2001.
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SUMMARY The overall goal for this review is to summarize the current body of knowledge about the structure and function of major known antigens of Streptococcus pneumoniae, a major gram-positive bacterial pathogen of humans. This information is then related to the role of these proteins in pneumococcal pathogenesis and in the development of new vaccines and/or other antimicrobial agents. S. pneumoniae is the most common cause of fatal community-acquired pneumonia in the elderly and is also one of the most common causes of middle ear infections and meningitis in children. The present vaccine for the pneumococcus consists of a mixture of 23 different capsular polysaccharides. While this vaccine is very effective in young adults, who are normally at low risk of serious disease, it is only about 60% effective in the elderly. In children younger than 2 years the vaccine is ineffective and is not recommended due to the inability of this age group to mount an antibody response to the pneumococcal polysaccharides. Antimicrobial drugs such as penicillin have diminished the risk from pneumococcal disease. Several pneumococcal proteins including pneumococcal surface proteins A and C, hyaluronate lyase, pneumolysin, autolysin, pneumococcal surface antigen A, choline binding protein A, and two neuraminidase enzymes are being investigated as potential vaccine or drug targets. Essentially all of these antigens have been or are being investigated on a structural level in addition to being characterized biochemically. Recently, three-dimensional structures for hyaluronate lyase and pneumococcal surface antigen A became available from X-ray crystallography determinations. Also, modeling studies based on biophysical measurements provided more information about the structures of pneumolysin and pneumococcal surface protein A. Structural and biochemical studies of these pneumococcal virulence factors have facilitated the development of novel antibiotics or protein antigen-based vaccines as an alternative to polysaccharide-based vaccines for the treatment of pneumococcal disease.
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Murphy, Clare, Donald Inverarity, Claire McGoldrick, Lindsay Mitchell, Pamela Paterson, Louise Thom, and Giles Edwards. "Treated Follicular Lymphoma, Recurrent Invasive Pneumococcal Disease, Nonresponsiveness to Vaccination, and a Unique Pneumococcus." Case Reports in Hematology 2012 (2012): 1–3. http://dx.doi.org/10.1155/2012/386372.
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A nonneutropenic patient with treated low-grade non-Hodgkin’s (Follicular) lymphoma and secondary hypogammaglobulinemia recovered from pneumococcal pneumonia and septicemia (serotype 7F; ST191) subsequent to influenza A H1N1 (2009). Both infections were potentially vaccine preventable. The patient then developed pneumococcal meningitis due to a serotype 35F pneumococcus with a unique Multilocus Sequence Type (ST7004) which was not vaccine preventable. Patient management was influenced by host predisposition to pneumococcal infection, antibiotic intolerance, and poor response to polysaccharide pneumococcal vaccine. Indirect immunofluorescence with anti-human immunoglobulin confirmed a poor or intermediate response to Pneumovax II. Prophylactic erythromycin was initiated, and immunoglobulin transfusions were also commenced as a preventive strategy. ST7004 is a single locus variant of ST1635 which has been associated with the serotype 35F capsule in England. Thespigene in ST7004, which differentiates it from ST1635, is the same as thespigene present in ST191 which could have arisen from the first disease episode suggesting that horizontal gene transfer may have occurred between different populations of pneumococci present within the patient in an attempt to evade vaccination selection pressure.
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Tasslimi, Azadeh, Erica J. Sison, Elizabeth Story, David Alland, Michele Burday, Susan Morrison, Sandhya Nalmas, et al. "Disappearance of Vaccine-Type Invasive Pneumococcal Disease and Emergence of Serotype 19A in a Minority Population with a High Prevalence of Human Immunodeficiency Virus and Low Childhood Immunization Rates." Clinical and Vaccine Immunology 16, no. 8 (June 10, 2009): 1256–59. http://dx.doi.org/10.1128/cvi.00140-09.
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ABSTRACT We analyzed the epidemiology of invasive pneumococcal disease (IPD) following introduction of pneumococcal conjugated vaccine in an urban population with a 2% human immunodeficiency virus (HIV) prevalence and history of low childhood immunization rates. We observed near-elimination of vaccine-type IPD. Substantial disease remains due to non-vaccine-type pneumococci, highlighting the need to increase pneumococcal immunization among HIV-infected adults.
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Klugman, Keith P. "Contribution of vaccines to our understanding of pneumococcal disease." Philosophical Transactions of the Royal Society B: Biological Sciences 366, no. 1579 (October 12, 2011): 2790–98. http://dx.doi.org/10.1098/rstb.2011.0032.
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Pneumonia is the leading cause of mortality in children in developing countries and is also the leading infectious cause of death in adults. The most important cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus pneumoniae , also known as the pneumococcus. It has thus become the leading vaccine-preventable cause of death and is a successful and diverse human pathogen. The development of conjugate pneumococcal vaccines has made possible the prevention of pneumococcal disease in infants, but has also elucidated aspects of pneumococcal biology in a number of ways. Use of the vaccine as a probe has increased our understanding of the burden of pneumococcal disease in children globally. Vaccination has also elucidated the clinical spectrum of vaccine-preventable pneumococcal infections; the identification of a biological niche for multiple pneumococcal serotypes in carriage and the differential invasiveness of pneumococcal serotypes; the impact of pneumococcal transmission among children on disease burden in adults; the role of carriage as a precursor to pneumonia; the plasticity of a naturally transformable pathogen to respond to selective pressure through capsular switching and the accumulation of antibiotic-resistance determinants; and the role of pneumococcal infections in hospitalization and mortality associated with respiratory viral infections, including both seasonal and pandemic influenza. Finally, there has been a recent demonstration that pneumococcal pneumonia in children may be an important cause of hospitalization for those with underlying tuberculosis.
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Papadatou, Ioanna, Irene Tzovara, and Paul Licciardi. "The Role of Serotype-Specific Immunological Memory in Pneumococcal Vaccination: Current Knowledge and Future Prospects." Vaccines 7, no. 1 (January 29, 2019): 13. http://dx.doi.org/10.3390/vaccines7010013.
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Streptococcus pneumoniae (S. pneumoniae, pneumococcus) is a major cause of morbidity and mortality worldwide. Achieving long-term immunity against S. pneumoniae through immunization is an important public health priority. Long-term protection after immunization is thought to rely both on protective serum antibody levels and immunological memory in the form of antigen-specific memory B cells (MBCs). Although the ability to achieve protective antibody levels shortly after pneumococcal vaccination has been well documented for the various infant immunization schedules currently in use worldwide, the examination of immunological memory in the form of antigen-specific MBCs has been much more limited. Such responses are critical for long-term protection against pneumococcal colonization and disease. This review summarizes the published literature on the MBC response to primary or booster immunization with either pneumococcal polysaccharide vaccine (PPV23) or pneumococcal conjugate vaccines (PCVs), aiming to elucidate the immunological mechanisms that determine the magnitude and longevity of vaccine protection against pneumococcus. There is evidence that PCVs induce the production of antigen-specific MBCs, whereas immunization with PPV23 does not result in the formation of MBCs. Increased understanding of the immunological factors that facilitate the induction, maintenance and recall of MBCs in response to pneumococcal vaccination could enable the use of MBC enumeration as novel correlates of protection against S. pneumoniae. Ongoing studies that examine MBC response to pneumococcal vaccination in high burden settings will be extremely important in our understanding of long-term protection induced by pneumococcal conjugate vaccines.
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Daniels, Calvin C., P. David Rogers, and Chasity M. Shelton. "A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens." Journal of Pediatric Pharmacology and Therapeutics 21, no. 1 (January 1, 2016): 27–35. http://dx.doi.org/10.5863/1551-6776-21.1.27.
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This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines.
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Wu, Kaifeng, Xuemei Zhang, Jing Shi, Nan Li, Dairong Li, Miao Luo, Ju Cao, et al. "Immunization with a Combination of Three Pneumococcal Proteins Confers Additive and Broad Protection against Streptococcus pneumoniae Infections in Mice." Infection and Immunity 78, no. 3 (December 28, 2009): 1276–83. http://dx.doi.org/10.1128/iai.00473-09.
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ABSTRACT Pneumococcal polysaccharide-based vaccines are effective in preventing pneumococcus infection; however, some drawbacks preclude their widespread use in developing and undeveloped countries. Here, we evaluated the protective effects of ATP-dependent caseinolytic protease (ClpP), pneumolysin mutant (ΔA146 Ply), putative lipoate-protein ligase (Lpl), or combinations thereof against pneumococcal infections in mice. Vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. In intraperitoneal challenge models with pneumococcal strain D39 (serotype 2), the most striking protection was obtained with the combination of the three antigens. Similarly, with the intranasal challenge models, (i) additive clearance of bacteria in lungs was observed for the combination of the three antigens and (ii) a combination vaccine conferred complete protection against intranasal infections of three of the four most common pneumococcal strains (serotypes 14, 19F, and 23F) and 80% protection for pneumococcal strain 6B. Even so, immunity to this combination could confer protection against pneumococcal infection with a mixture of four serotypes. Our results showed that the combination vaccine was as effective as the currently used vaccines (PCV7 and PPV23). These results indicate that system immunization with the combination of pneumococcal antigens could provide an additive and broad protection against Streptococcus pneumoniae in pneumonia and sepsis infection models.
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Trukhin, V. P., A. E. Evtushenko, E. L. Salimova, A. D. Konon, M. R. Khaitov, and V. A. Merkulov. "Analysis of pneumococcal serotypes distribution to determine a model composition for a Russian pneumococcal conjugate vaccine." Biological Products. Prevention, Diagnosis, Treatment 22, no. 2 (June 2, 2022): 124–41. http://dx.doi.org/10.30895/2221-996x-2022-22-2-124-141.
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Diseases caused by Streptococcus pneumoniae, as well as antibiotic resistance of its serotypes, are the leading cause of death amongst children worldwide. To prevent pneumococcal infection, the population is immunised with conjugate vaccines containing different amounts of polysaccharides of certain serotypes. Development of a full-cycle Russian vaccine is vital because the active pharmaceutical ingredients for the vaccines registered in the Russian Federation are produced abroad, and only the final stages of production of vaccines of this group are performed in the territory of the Russian Federation. Considering the phenomenon of serotype replacement associated with the long-term widespread use of pneumococcal conjugate vaccines, it is necessary to carefully select the serotype composition for the new vaccine. The aim of this work was to analyse the serotype distribution of pneumococci in the Russian Federation and other countries in order to select optimal serotypes for the Russian vaccine for human use, taking into account vaccination schedules for each age group. This review presents an analysis of the pneumococcal serotype distribution in the Russian Federation in the pre-vaccination era, as well as after the introduction of routine vaccination. In addition, the review includes data on the serotype distribution in the Eurasian Economic Union countries. The authors described a model composition containing at least sixteen serotypes. It will increase effectiveness of immune protection of the population, providing a more complete coverage of serotypes, considering their prevalence in the Russian Federation. Based on the analysis, the serotype composition for the sixteen-valent pneumococcal conjugate vaccine is proposed for further production and preclinical and clinical trials. A new Russian pneumococcal conjugate vaccine will ensure vaccination of all population groups within the National Immunisation Schedule of the Russian Federation.
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Tóthpál, Adrienn, and Orsolya Dobay. "Drastic changes in serotypes of carried pneumococci due to an increased vaccination rate in Hungary." Orvosi Hetilap 153, no. 26 (July 2012): 1031–34. http://dx.doi.org/10.1556/oh.2012.29354.
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Introduction of the conjugate pneumococcal vaccine into the voluntary childhood vaccine program in Hungary in April 2009 resulted in a sharp increase of the vaccination rate. However, changes in serotypes as a consequence of vaccination should be considered. Aims: The aim of the authors was to compare pneumococci isolated from children with high-level and low-level vaccination rates. Methods: Nasal specimens from 854 children attending 20 nurseries at various locations in Hungary have been collected since 2009. The serotypes, antibiotic susceptibility and genetic relatedness of the isolated pneumococci were determined. Results: 324 strains were isolated, and the carriage rate was 37.94%. The strains were sensitive to most antibiotics, except for macrolides. A definite suppression of vaccine types was detected during these 3 years, from the initial 78.85% to 35.30%. Conclusions: The authors conclude that the results reflect the efficacy of the vaccine, which underlines the need for the inclusion of pneumococcal vaccine into the list of obligatory vaccines. Orv. Hetil., 2012, 153, 1031–1034.
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Korona-Glowniak, Izabela, and Anna Malm. "Characteristics ofStreptococcus pneumoniaeStrains Colonizing Upper Respiratory Tract of Healthy Preschool Children in Poland." Scientific World Journal 2012 (2012): 1–10. http://dx.doi.org/10.1100/2012/732901.
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Antibiotic resistant and invasive pneumococci may spread temporally and locally in day care centers (DCCs). We examined 267 children attending four DCCs located in the same city and 70 children staying at home in three seasons (autumn, winter, and spring) to determine prevalence, serotype distribution, antibiotic resistance patterns, and transmission of pneumococcal strains colonizing upper respiratory tract of healthy children without antipneumococcal vaccination. By pheno- and genotyping, we determined clonality of pneumococci, including drug-resistant strains. The average carriage of pneumococci in three seasons was 38.2%. 73.4% and 80.4% of the isolates belonged to serotypes present in 10- and 13-valent conjugate vaccine, respectively. Among the pneumococcal strains, 33.3% were susceptible to all antimicrobial tested and 39.2% had decreased susceptibility to penicillin. Multidrug resistance was common (35.7%); 97.5% of drug-resistant isolates represented serotypes included to 10- and 13-valent conjugate vaccine. According to BOX-PCR, clonality definitely was observed only in case of serotype 14. Multivariate analysis determined DCC attendance as strongly related to pneumococcal colonization in all three seasons, but important seasonal differences were demonstrated. In children attending DCCs, we observed dynamic turnover of pneumococcal strains, especially penicillin nonsusceptible and multidrug resistant, which were mostly distributed among serotypes included to available pneumococcal conjugate vaccines.
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Kulohoma, Benard W., Katherine Gray, Arox Kamng'ona, Jennifer Cornick, Stephen D. Bentley, Robert S. Heyderman, and Dean B. Everett. "Piliation of Invasive Streptococcus pneumoniae Isolates in the Era before Pneumococcal Conjugate Vaccine Introduction in Malawi." Clinical and Vaccine Immunology 20, no. 11 (September 11, 2013): 1729–35. http://dx.doi.org/10.1128/cvi.00403-13.
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ABSTRACTThe pneumococcal pilus has been shown to be an important determinant of adhesion and virulence in mouse models of colonization, pneumonia, and bacteremia. A pilus is capable of inducing protective immunity, supporting its inclusion in next-generation pneumococcal protein vaccine formulations. Whether this vaccine target is common among pneumococci in sub-Saharan Africa is uncertain. To define the prevalence and genetic diversity of type I and II pili among invasive pneumococci in Malawi prior to the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into routine childhood immunization, we examined 188Streptococcus pneumoniaeisolates collected between 2002 and 2008 (17% serotype 1). In this region of high disease burden, we found a low frequency of invasive piliated pneumococci (14%) and pilus gene sequence diversity similar to that seen previously in multiple global pneumococcal lineages. All common serotypes with pilus were covered by PCV13 and so we predict that pilus prevalence will be reduced in the Malawian pneumococcal population after PCV13 introduction.
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Kostyukova, N. N., and V. A. Bekhalo. "Pneumococcal Polysaccharide Conjugated Vaccines and the Problem of Changing Circulating Serotypes of Pneumococcus." Epidemiology and Vaccinal Prevention 22, no. 5 (November 11, 2023): 110–20. http://dx.doi.org/10.31631/2073-3046-2023-22-5-110-120.
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Relevance. In 2007, WHO recommended pneumococcal conjugate vaccines (PCV) be included in national immunization schedules for young children. By 2020, 145 countries, including Russia, were using PCV. Aims. To identify vaccines with high epidemiological and immunological efficacy against various forms of pneumococcal infection, including carriage. Conclusions. It has been shown that PCV has high epidemiological and immunological efficacy against various forms of pneumococcal infection, including carriage. It was revealed that the mass use of PCV, leading to the elimination of "vaccine" serotypes, is simultaneously accompanied by the spread of cases of infection due to serotypes not included in vaccines, which significantly reduces the positive effect of vaccination. This requires frequent replacement of serotype polysaccharides in the vaccine in accordance with the serotypes of circulating strains. An alternative to PCV can be vaccines based on pneumolysin, surface pneumococcal proteins, whole – cell and live attenuated, protein-based subunit vaccines, etc. vaccine variants.
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Masomian, Malihe, Zuleeza Ahmad, Lai Ti Gew, and Chit Laa Poh. "Development of Next Generation Streptococcus pneumoniae Vaccines Conferring Broad Protection." Vaccines 8, no. 1 (March 17, 2020): 132. http://dx.doi.org/10.3390/vaccines8010132.
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Streptococcus pneumoniae is a major pathogen causing pneumonia with over 2 million deaths annually, especially in young children and the elderly. To date, at least 98 different pneumococcal capsular serotypes have been identified. Currently, the vaccines for prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes and are unable to protect against non-vaccine serotypes and unencapsulated S. pneumoniae. This has led to a rapid increase in antibiotic-resistant non-vaccine serotypes. Hence, there is an urgent need to develop new, effective, and affordable pneumococcal vaccines, which could cover a wide range of serotypes. This review discusses the new approaches to develop effective vaccines with broad serotype coverage as well as recent development of promising pneumococcal vaccines in clinical trials. New vaccine candidates are the inactivated whole-cell vaccine strain (Δpep27ΔcomD mutant) constructed by mutations of specific genes and several protein-based S. pneumoniae vaccines using conserved pneumococcal antigens, such as lipoprotein and surface-exposed protein (PspA). Among the vaccines in Phase 3 clinical trials are the pneumococcal conjugate vaccines, PCV-15 (V114) and 20vPnC. The inactivated whole-cell and several protein-based vaccines are either in Phase 1 or 2 trials. Furthermore, the recent progress of nanoparticles that play important roles as delivery systems and adjuvants to improve the performance, as well as the immunogenicity of the nanovaccines, are reviewed.
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Yuki, Yoshikazu, Il Kong, Ayuko Sato, Tomonori Nochi, Mio Mejima, Shiho Kurokawa, Tomoko Hiroiwa, et al. "Adjuvant-free nanogel-based PspA nasal vaccine for the induction of protective immunity against Pneumococcus (166.7)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 166.7. http://dx.doi.org/10.4049/jimmunol.188.supp.166.7.
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Abstract To establish strategically effective and attractive vaccine against pneumococcal respiratory infections, combining the current knowledge and technology for common antigen throughout pneumococcal strains and the new delivery system is essential. Here, we introduce a new pneumococcal nasal vaccine using the advantages of Pneumococcal surface protein A (PspA) antigen and a new adjuvant-free intranasal vaccine-delivery system with a nanometer-sized hydrogel (nanogel) consisting of a cationic type of cholesteryl group-bearing pullulan (cCHP). Nanogel-based PspA nasal vaccination induced high levels of antigen-specific serum IgG, and nasal and bronchial secretory IgA (SIgA) antibodies. The levels of PspA-specific antibodies were as high as those in mice nasally immunized with PspA and mucosal adjuvant, cholera toxin. The nanogel induced PspA-specific immune responses provided protective immunity against the lethal challenge with Streptococcus pneumoniae Xen10. Nanogel-PspA vaccinated group thus had less numbers of pneumococcus on the surface of the bronchial mucosa, and perfectly protected from the pneumococcal invasion of the lung parenchyma. These results demonstrate the effectiveness of the nanogel-based PspA nasal vaccine system as an adjuvant free mucosal vaccine against the respiratory infection of pneumococcus.
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Robinson, Tara M., and Sophie M. Lanzkron. "Standard Definitions of Pneumococcal Immunity May Not Accurately Predict Protection in Adults with Sickle Cell Disease." Blood 134, Supplement_1 (November 13, 2019): 1014. http://dx.doi.org/10.1182/blood-2019-126056.
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Patients with sickle cell disease (SCD) are now routinely living into adulthood, but SCD has deleterious effects on multiple organ systems which can lead to increased complications from illness. SCD patients generally auto-splenectomize in childhood secondary to infarctions from their hemoglobinopathy, thus increasing their risk of infection with encapsulated organisms such as S. pneumoniae. Although there are data to demonstrate that vaccination has drastically decreased the incidence of invasive pneumococcal disease (i.e. bacteremia or meningitis) in children, the situation for adults is less clear. There are no data to guide the decision to use conjugated and/or polysaccharide pneumococcus vaccines in adults. In addition, there are few data available on the efficacy of pneumococcal vaccination on non-invasive disease such as pneumonia. Two landmark studies have demonstrated the efficacy of polysaccharide-based pneumococcal vaccines in the general adult population to be approximately 56%. However, there are data to suggest that immune responses in SCD patients may be impaired, and thus responses to vaccines may be suboptimal. Current sickle cell guidelines for pneumococcal vaccination, which are based on expert opinion, recommend one dose of Prevnar 13 (conjugated vaccine) followed by one dose of Pneumovax 23 (polysaccharide vaccine) with a booster of Pneumovax 23 at age 65. However, some clinicians choose to vaccinate every 5 years due to fear of waning immunity. There is a lack of data on which to base guidelines, and there are also no data nor any guidelines to help decide if patients needs additional boosters of vaccine. Besides the potential for suboptimal immune responses in sickle cell patients, the standard definition used to define a responder to pneumococcal vaccine may not translate to protection from disease in the real world. Most studies define a responder as having a protective titer to 50-70% of the serotypes tested. However, this definition has no consideration for the prevalence of serotypes causing disease in the community. Therefore it's possible to have a patient who responds to 50% of the serotypes in the assay and is considered immune, but if those serotypes are all uncommon, then the patient may still be at high risk for serious disease. Determining a better way to identify patients at risk for pneumococcal disease and optimizing vaccination strategies to prevent this disease would help to improve the lives of patients. We performed a retrospective study to investigate immunity to pneumococcus in adult patients with SCD. We used the electronic medical record and collected data on patient demographics, sickle cell genotype, dates of previous pneumococcal vaccination (both conjugated and polysaccharide vaccines), quantitative antibody levels to individual pneumococcus serotypes, as well as information on comorbidities. In our sample of n=28 patients with SCD and available antibody data, 68% met a commonly accepted definition of immunity, which we defined by having an antibody concentration ≥ 1 mcg/mL for at least 50% of any of the serotypes tested. Immunity was inversely correlated with time from last pneumococcal vaccination, and it did not matter whether the most recent vaccine was the conjugated or polysaccharide product (Fig 1a). We then sought to analyze the data with consideration for the prevalence of various serotypes based on epidemiologic data published in The Lancet Infectious Diseases15,301-309 (2015). Interestingly, only 21% of patients who met the traditional definition of being a vaccine responder had protective titers to all 3 of the most prevalent serotypes tested, and 10% of patients who would traditionally be characterized as vaccine responders did not have sufficient antibody production to any of the 3 most prevalent serotypes tested in the assay (Fig. 1b, left). Of the 9 patients who were categorized as vaccine nonresponders based on the traditional definition, one subject was actually immune to all 3 of the most common serotypes in the community (Fig 1b, right), suggesting that he may actually be well-covered for pneumococcus in the real world. This study raises concern about the definition of immunity following vaccination, and highlights the challenge to identify which patients are at risk for disease. Future studies should examine how immunity wanes post vaccination and how the lack of immunity to prevalent serotypes might lead to clinical disease. Disclosures Lanzkron: Pfizer: Research Funding; Global Blood Therapeutics: Research Funding; Ironwood: Research Funding; HRSA: Research Funding; NIH: Research Funding; PCORI: Research Funding.
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Keller, Lance E., Xiao Luo, Justin A. Thornton, Keun-Seok Seo, Bo Youn Moon, D. Ashley Robinson, and Larry S. McDaniel. "Immunization with Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Provides Protection in a Mouse Model of Colonization." Clinical and Vaccine Immunology 22, no. 11 (August 26, 2015): 1146–53. http://dx.doi.org/10.1128/cvi.00456-15.
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ABSTRACTCurrent vaccinations are effective against encapsulated strains ofStreptococcus pneumoniae, but they do not protect against nonencapsulatedStreptococcus pneumoniae(NESp), which is increasing in colonization and incidence of pneumococcal disease. Vaccination with pneumococcal proteins has been assessed for its ability to protect against pneumococcal disease, but several of these proteins are not expressed by NESp. Pneumococcal surface protein K (PspK), an NESp virulence factor, has not been assessed for immunogenic potential or host modulatory effects. Mammalian cytokine expression was determined in anin vivomouse model and in anin vitrocell culture system. Systemic and mucosal mouse immunization studies were performed to determine the immunogenic potential of PspK. Murine serum and saliva were collected to quantitate specific antibody isotype responses and the ability of antibody and various proteins to inhibit epithelial cell adhesion. Host cytokine response was not reduced by PspK. NESp was able to colonize the mouse nasopharynx as effectively as encapsulated pneumococci. Systemic and mucosal immunization provided protection from colonization by PspK-positive (PspK+) NESp. Anti-PspK antibodies were recovered from immunized mice and significantly reduced the ability of NESp to adhere to human epithelial cells. A protein-based pneumococcal vaccine is needed to provide broad protection against encapsulated and nonencapsulated pneumococci in an era of increasing antibiotic resistance and vaccine escape mutants. We demonstrate that PspK may serve as an NESp target for next-generation pneumococcal vaccines. Immunization with PspK protected against pneumococcal colonization, which is requisite for pneumococcal disease.
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Mirzaeva, A. R., T. V. Kulichenko, O. I. Lebedeva, Z. A. Alacheva, T. G. Kuznetsova, N. M. Alyabyeva, E. A. Brzhozovskaya, and N. A. Mayanskiy. "NASOPHARYNGEAL CARRIAGE OF STREPTOCOCCUS PNEUMONIAE IN CHILDREN UNDER 5 YEARS OF AGE AFTER INTRODUCTION OF PNEUMOCOCCAL CONJUGATE VACCINATION IN THE REPUBLIC OF KHAKASSIA." Russian Pediatric Journal 22, no. 4 (August 15, 2019): 196–204. http://dx.doi.org/10.18821/1560-9561-2019-22-4-196-204.
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Introduction The dynamic study of the serotype composition and the level of antibiotic resistance of S. pneumoniae in different regions is the most important component of the control of pneumococcal infections (PI). The aim of the study was to analyze the serotype composition of S. pneumoniae isolated from the nasopharynx in children under 5 years of age, as well as to assess the sensitivity of pneumococci to antimicrobials, depending on the vaccination status and previous antibacterial therapy. Materials and methods A multicenter cohort study of nasopharyngeal carriage, serotype diversity and sensitivity to pneumococcal antibiotics were conducted in 13 centers in the Republic of Khakassia. Results 498 nasopharyngeal smears were collected, pneumococcus was isolated in 51.6% of cases. PI vaccination coverage in the cohort was 67.2%. The carriage of pneumococcus did not differ in children depending on their vaccination status (52.3% in vaccinated and 52.2% in unvaccinated). There was revealed a significant decrease in the carrier rate of pneumococcal vaccine serotypes in the cohort of vaccinated children compared with unvaccinated (17.6% vs 34.7%, p <0.05). High resistance of S. pneumoniae to penicillin (38.6%), macrolides (29.7%), trimethoprim/sulfamethoxazole (28.6%) was found. Amoxicillin resistance accounted for 20.8%, and ceftriaxone - 16.6%. Antibiotic-resistant vaccine serotypes were twofold more common. Conclusion The introduction of mass vaccination against PI in the country does not reduce the nasopharyngeal carriage of pneumococcus, but significantly reduces the circulation of vaccine serotypes, including strains resistant to antibiotics.
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Masala, G. L., M. Lipsitch, C. Bottomley, and S. Flasche. "Exploring the role of competition induced by non-vaccine serotypes for herd protection following pneumococcal vaccination." Journal of The Royal Society Interface 14, no. 136 (November 2017): 20170620. http://dx.doi.org/10.1098/rsif.2017.0620.
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The competitive pressure from non-vaccine serotypes may have helped pneumococcal conjugate vaccines (PCVs) to limit vaccine-type (VT) serotype prevalence. We aimed to investigate if, consequently, the indirect protection of vaccines targeting most pneumococcal serotypes could fall short of the profound effects of current formulations. We compared three previously described pneumococcal models harmonized to simulate 20 serotypes with a combined pre-vaccination prevalence in children younger than 5-years-old of 40%. We simulated vaccines of increasing valency by adding serotypes in order of their competitiveness and explored their ability to reduce VT carriage by 95% within 10 years after introduction. All models predicted that additional valency will reduce indirect vaccine effects and hence the overall vaccine impact on carriage both in children and adults. Consequently, the minimal effective coverage (efficacy against carriage×vaccine coverage) needed to eliminate VT carriage increased with increasing valency. One model predicted this effect to be modest, while the other two predicted that high-valency vaccines may struggle to eliminate VT pneumococci unless vaccine efficacy against carriage can be substantially improved. Similar results were obtained when settings of higher transmission intensity and different PCV formulations were explored. Failure to eliminate carriage as a result of increased valency could lead to overall decreased impact of vaccination if the disease burden caused by the added serotypes is low. Hence, a comparison of vaccine formulations of varying valency, and pan-valent formulations in particular, should consider the invasiveness of targeted serotypes, as well as efficacy against carriage.
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Alghamdi, Saad, Muhammad Umar Khayam Sahibzada, Nashwa T. Shesha, Akhmed Aslam, Ahmed Kabrah, Banan Atwah, Elshiekh B. Khidir, et al. "Pneumococcal Surface Protein A: A Promising Candidate for the Next Generation of Pneumococcal Vaccines." Cellular and Molecular Biology 67, no. 4 (January 2, 2022): 289–98. http://dx.doi.org/10.14715/cmb/2021.67.4.32.
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Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.
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Patel, Sweta M., Yazdani B. Shaik-Dasthagirisaheb, Morgan Congdon, Rebecca R. Young, Mohamed Z. Patel, Tiny Mazhani, Sefelani Boiditswe, et al. "Evolution of pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine." PLOS ONE 17, no. 1 (January 5, 2022): e0262225. http://dx.doi.org/10.1371/journal.pone.0262225.
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Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.
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Menéndez, Rosario, Antoni Torres, Pedro Pablo España, Jose Alberto Fernández-Villar, José María Marimón, Raúl Méndez, Catia Cilloniz, et al. "Pneumococcal Serotypes Associated with Community-Acquired Pneumonia Hospitalizations in Adults in Spain, 2016–2020: The CAPA Study." Microorganisms 11, no. 11 (November 16, 2023): 2781. http://dx.doi.org/10.3390/microorganisms11112781.
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Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.
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Briles, David E., Rebecca Creech Tart, Edwin Swiatlo, Joseph P. Dillard, Patricia Smith, Kimberly A. Benton, Beth A. Ralph, et al. "Pneumococcal Diversity: Considerations for New Vaccine Strategies with Emphasis on Pneumococcal Surface Protein A (PspA)." Clinical Microbiology Reviews 11, no. 4 (October 1, 1998): 645–57. http://dx.doi.org/10.1128/cmr.11.4.645.
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SUMMARY Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.
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Lebon, Ankie, Nelianne J. Verkaik, Joost A. M. Labout, Corné P. de Vogel, Herbert Hooijkaas, Henri A. Verbrugh, Willem J. B. van Wamel, et al. "Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study." Infection and Immunity 79, no. 4 (January 31, 2011): 1680–87. http://dx.doi.org/10.1128/iai.01379-10.
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ABSTRACTThe currently available pneumococcal vaccines do not protect against all serotypes ofStreptococcus pneumoniae. A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months (n= 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.
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Gruber, I. M., O. M. Kukina, N. B. Egorova,, and O. V. Zhigunova. "Different Technologies for Obtaining Pneumococcal Immunogens." Epidemiology and Vaccinal Prevention 20, no. 1 (March 13, 2021): 76–91. http://dx.doi.org/10.31631/2073-3046-2021-20-1-76-91.
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Relevance. The worldwide use of pneumococcal vaccines, in particular conjugated vaccines (PCV), has led to a significant reduction in the incidence of invasive pneumococcal diseases in both vaccinated children and unvaccinated people of all ages. However, "non-vaccine" serotypes and capsule-free (non-typed) strains have become the main causes of pneumococcal disease, as with carriage, with an increase in antibiotic resistance. This requires new approaches in the development of vaccines that can lead to serotype-independent protection, especially in children, the elderly and immunocompromised people. The pneumococcal vaccine should protect against a wide range of serotypes, induce mucosal and systemic immunity, and reduce primary nasal colonization, as well as invasive forms. Aim. The review is devoted to the analysis of experimental development of innovative vaccines based on protective protein antigens (PPV), including in combination with capsular polysaccharides, using adjuvants or antigen delivery systems, as well as inactivated whole cell preparations (WCV) and live attenuated vaccines. Particular attention is paid to the methods of mucosal immunization, taking into account the tropism of pneumococcus in relation to the mucous membranes of the upper and lower respiratory tract. Conclusion. At this stage, the most developed and promising are drugs based on bacterial lysates (PWCV) and protective protein antigens (PspA, dPly), as well as these antigens mixed with adjuvants, and, possibly, with some etiologically most significant capsular polysaccharides.
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Morton, Ben, Sarah Burr, Kondwani Jambo, Jamie Rylance, Marc Y. R. Henrion, Ndaziona Peter Banda, Edna Nsomba, et al. "A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study." Wellcome Open Research 5 (February 11, 2020): 25. http://dx.doi.org/10.12688/wellcomeopenres.15689.1.
Full textAbstract:
Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and demonstrate reduced effectiveness against mucosal colonisation. As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants. We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice. The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.
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Morton, Ben, Sarah Burr, Kondwani Jambo, Jamie Rylance, Marc Y. R. Henrion, Ndaziona Peter Banda, Edna Nsomba, et al. "A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study." Wellcome Open Research 5 (April 14, 2020): 25. http://dx.doi.org/10.12688/wellcomeopenres.15689.2.
Full textAbstract:
Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and demonstrate reduced effectiveness against mucosal colonisation. As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants. We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice. The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.
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Morais, Texeira, and Suarez. "Next-Generation Whole-Cell Pneumococcal Vaccine." Vaccines 7, no. 4 (October 16, 2019): 151. http://dx.doi.org/10.3390/vaccines7040151.
Full textAbstract:
Streptococcus pneumoniae remains a major public health hazard. Although Pneumococcal Conjugate Vaccines (PCVs) are available and have significantly reduced the rate of invasive pneumococcal diseases, there is still a need for new vaccines with unlimited serotype coverage, long-lasting protection, and lower cost to be developed. One of the most promising candidates is the Whole-Cell Pneumococcal Vaccine (WCV). The new generation of whole-cell vaccines is based on an unencapsulated serotype that allows the expression of many bacterial antigens at a lower cost than a recombinant vaccine. These vaccines have been extensively studied, are currently in human trial phase 1/2, and seem to be the best treatment choice for pneumococcal diseases, especially for developing countries.
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Dayie, Nicholas TKD, Michael Baffuor-Asare, Appiah-Korang Labi, Noah Obeng-Nkrumah, Edeghonghon Olayemi, Margaret Lartey, Hans-Christian Slotved, and Eric S. Donkor. "Epidemiology of Pneumococcal Carriage among HIV-Infected Individuals in the Conjugate Vaccine Era: A Study in Southern Ghana." BioMed Research International 2019 (February 13, 2019): 1–8. http://dx.doi.org/10.1155/2019/3427174.
Full textAbstract:
Carriage of pneumococcus is considered as the precursor for development of pneumococcal disease. In sub-Saharan Africa, very little research has been done on the pneumococcus in relation to people with HIV infection in the era of pneumococcal conjugate vaccines. This study investigated pneumococcal carriage among HIV/AIDS patients in southern Ghana to determine the prevalence, risk factors, serotypes and antibiotic resistance of the organism. This was a cross sectional study involving 245 HIV/AIDS patients recruited from Korle Bu Teaching Hospital and Princess Marie Louis Hospital in Accra from November 2016 to March 2017. Epidemiological data on demographic, household and clinical features of the study participants were collected. Nasopharyngeal (NP) swabs were also collected from the study participants and cultured for Streptococcus pneumoniae; the isolates were serotyped by latex agglutination and Quellung reaction. Antimicrobial disc susceptibility was performed on the isolates, and antibiotics tested included tetracycline, erythromycin, cotrimoxazole, levofloxacin, oxacillin and ceftriaxone. Prevalence of pneumococcal carriage among the study participants was 11% (95% CI: 7.4 to 15.6); carriage among children and adults was 25% (95% CI: 14% to 38.9%) and 7.3% (95% CI: 4% to 11.9%) respectively. School attendance (p=0.001) and history of pneumococcal disease in the past year (p=0.001) were significantly associated with pneumococcal carriage. The most prevalent pneumococcal serotypes carried by the study participants were 19A (15.4%) and 23F (15.4%). Serotype coverage of the various pneumococcal vaccines were PCV10 (23.1%), PCV13 (42.3%) and PPV23 (50%). The prevalence of pneumococcal multidrug resistance was 18.5%. In conclusion, pneumococcal carriage among HIV-infected children was three-fold higher compared to carriage among HIV-infected adults. Pneumococcal carriage among both HIV-infected children and adults in the study area tends to be characterized by a predominance of non-vaccine serotypes and a considerable level of multidrug resistance.
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Thong, Bernard Yu-Hor, Ruby Pawankar, Hae-Sim Park, and Amir Hamzah Abdul Latiff. "Evaluating immune responses to pneumococcal vaccines." Asia Pacific Allergy 13, no. 3 (September 2023): 127–31. http://dx.doi.org/10.5415/apallergy.0000000000000114.
Full textAbstract:
Streptococcus pneumoniae (pneumococcus) is a significant cause of bacterial infections ranging from mild infections affecting the respiratory tract such as otitis media and sinusitis to severe diseases including bacteremia, pneumonia, and invasive pneumococcal disease (IPD) (eg, meningitis, septic arthritis, and endocarditis). Pneumococcal vaccines were first developed in the 1970s as capsular pneumococcal polysaccharide vaccines, which were T-cell independent and hence lacked immunologic memory. Subsequently in the year 2000, pneumococcal conjugate vaccines (PCV) conjugated to a protein to increase immunogenicity were developed and made commercially available. The increasing number of pneumococcal serotypes identified and the expanding pipeline of PCV vaccines with improved immunogenicity have significantly reduced the morbidity and mortality associated with IPD in high-risk patients. Pneumococcal vaccines also play an important role in the diagnosis and immunophenotyping of children and adults with inborn errors of immunity (IEI) given the increasing diversity/heterogeneity of IEI presenting with primary and/or specific antibody deficiency. Other than the quantitation of serotype levels in routine clinical care, other measurements of immune response including the functional activity of antibodies, antibody avidity, cell-mediated immunity, and immunological memory remain limited to clinical trials during vaccine development.
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Belocerkovskaja, Yulia G., A. G. Romanovskih, and E. A. Styrt. "Pneumococcal vaccine in adults reduces the risk of infections caused by Streptococcus pneumoniae." Clinical Medicine (Russian Journal) 94, no. 1 (February 19, 2016): 61–66. http://dx.doi.org/10.18821/0023-2149-2016-94-1-61-66.
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Streptococcus pneumoniae is a major cause of severe disease worldwide, particularly in the risk population. Two pneumococcal vaccines are currently available for specific prevention of pneumococcal infections among adults in Russia: a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13). The article describes modern views on the effectiveness and safety of two pneumococcal vaccines in adults with underlying medical conditions and adults aged ≥65 years and provides current recommendations for routine use of PPSV23 and PCV13 among persons included in the risk group.
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Deng, James Z., Zhifeng Chen, James Small, Yue Yuan, Kara Cox, Aimin Tang, Jeanette Roman, et al. "Identification and Quantification of a Pneumococcal Cell Wall Polysaccharide by Antibody-Enhanced Chromatography Assay." Vaccines 12, no. 5 (April 28, 2024): 469. http://dx.doi.org/10.3390/vaccines12050469.
Full textAbstract:
Multivalent pneumococcal vaccines have been developed successfully to combat invasive pneumococcal diseases (IPD) and reduce the associated healthcare burden. These vaccines employ pneumococcal capsular polysaccharides (PnPs), either conjugated or unconjugated, as antigens to provide serotype-specific protection. Pneumococcal capsular polysaccharides used for vaccine often contain residual levels of cell wall polysaccharides (C-Ps), which can generate a non-serotype specific immune response and complicate the desired serotype-specific immunity. Therefore, the C-P level in a pneumococcal vaccine needs to be controlled in the vaccine process and the anti C-P responses need to be dialed out in clinical assays. Currently, two types of cell-wall polysaccharide structures have been identified: a mono-phosphocholine substituted cell-wall polysaccharide C-Ps1 and a di-phosphocholine substituted C-Ps2 structure. In our effort to develop a next-generation novel pneumococcal conjugate vaccine (PCV), we have generated a monoclonal antibody (mAb) specific to cell-wall polysaccharide C-Ps2 structure. An antibody-enhanced HPLC assay (AE-HPLC) has been established for serotype-specific quantification of pneumococcal polysaccharides in our lab. With the new anti C-Ps2 mAb, we herein extend the AE-HPLC assay to the quantification and identification of C-Ps2 species in pneumococcal polysaccharides used for vaccines.
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KYAW, M. H., B. WAYNE, J. CHALMERS, I. G. JONES, and H. CAMPBELL. "Influenza and pneumococcal vaccine distribution and use in primary care and hospital settings in Scotland: coverage, practice and policies." Epidemiology and Infection 128, no. 3 (June 2002): 445–55. http://dx.doi.org/10.1017/s0950268802006891.
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A survey of the coverage, distribution and the factors associated with use of influenza and pneumococcal vaccines among general practitioners (GPs) in primary care and in hospital settings was carried out in 53 general practices in Scotland taking part in the ‘Continuous Morbidity Recording’ (CMR) programme. The annual vaccine distribution increased substantially among 53 general practices from 1993 to 1999 and in Scotland as a whole from 1984 to 1999. From the questionnaire, overall coverage was 43% (95% CI 38–48) for influenza vaccine in the 2000–1 season and 13% (95% CI 9–16) for pneumococcal vaccine in the last 5 year period, in high-risk patients recommended for these vaccines by the Department of Health (DoH). Influenza vaccine coverage was highest in the elderly (65 years of age and above) at 62% (95% CI 59–74). Although pneumococcal vaccination is not currently recommended for all elderly, coverage of this vaccine was also higher in this group (22%, 95% CI 16–29). In the majority of patients (influenza vaccine, 98% and pneumococcal vaccine, 94%), vaccination was carried out in general practice. Only 2% of patients had received pneumococcal vaccination in a hospital setting. The level of influenza and pneumococcal vaccination varied with the level of deprivation. Most GPs considered that the responsibility for influenza and pneumococcal vaccination lay with them. Forty-five percent of GPs reported having a written policy with set target for influenza vaccination and 11% for pneumococcal vaccination.
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Kostinov, A. M., M. P. Kostinov, and C. V. Mashilov. "Antagonism between pneumococcal vaccines and COVID-19." Meditsinskiy sovet = Medical Council, no. 17 (November 22, 2020): 66–73. http://dx.doi.org/10.21518/2079-701x-2020-17-66-73.
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The review examines the clinical and epidemiological links between COVID-19 and pneumonia. At the same time, both general patterns linking viral respiratory infections and bacterial infections of the lower respiratory tract are discussed, as well as recent data relating directly to COVID-19. The clinical aspects of secondary infections, the peculiarities of their etiology, course and outcomes are analyzed separately. The publication provides a short essay on the history of the development of vaccines against pneumococcal infection. The current vaccines against pneumococcal infection are described, their brief characteristics and individual characteristics are given, their clinical and immunological advantages and disadvantages are analyzed. The data on the effectiveness of vaccine prophylaxis using pneumococcal vaccine are presented. The specific and nonspecific effects of vaccine prophylaxis both at the population level and at the level of an individual organism as a whole and in particular when using vaccines against pneumococci are considered separately. Data on the putative biochemical and molecular mechanisms of these effects are presented. Based on the data presented, the need for the use of pneumococcal vaccines in the prevention of the spread of the SARS-Cov2 virus, the prevention of complications of COVID-19 and the rehabilitation of patients who have undergone this infection is substantiated. When considering the role of pneumococcal vaccines in the rehabilitation of patients who have undergone COVID-19, their potential is analyzed both in accelerating the restoration of the normal functioning of the immune system and in the prevention of superinfections. The ways of further research in this direction are outlined, which include the development of protocols for certain groups of patients with concomitant diseases and immuno-compromised contingents. In this direction, the role of a thorough and comprehensive study of the immunological and clinical indicators of this category of persons is emphasized.
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Fay, Emily E., Kara K. Hoppe, Jay Schulkin, and Linda O. Eckert. "Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination." Infectious Diseases in Obstetrics and Gynecology 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/1752379.
Full textAbstract:
Objective.The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination.Methods.We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question.Results.238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination.Conclusion. OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed.
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Subesinghe, Sujith, Katie Bechman, Andrew I. Rutherford, David Goldblatt, and James B. Galloway. "A Systematic Review and Metaanalysis of Antirheumatic Drugs and Vaccine Immunogenicity in Rheumatoid Arthritis." Journal of Rheumatology 45, no. 6 (March 15, 2018): 733–44. http://dx.doi.org/10.3899/jrheum.170710.
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Objective.Vaccination is a key strategy to reduce infection risk in patients with rheumatoid arthritis (RA) and is advocated in internationally recognized rheumatology society guidelines. The aim was to evaluate to the effect of antirheumatic drugs on influenza and pneumococcal vaccine immunogenicity.Methods.We conducted a systematic literature review and metaanalysis comparing the humoral response to influenza (pandemic and seasonal trivalent subunit vaccines) and pneumococcal (23-valent pneumococcal polysaccharide vaccine, 7- and 13-valent pneumococcal conjugated vaccines) vaccination in adult patients with RA treated with antirheumatic drugs. Vaccine immunogenicity was assessed by seroprotection rates measured 3 to 6 weeks postimmunization. Risk ratios (RR) and 95% CI were pooled.Results.Nine studies were included in the metaanalysis (7 studies investigating antirheumatic drug exposures and influenza humoral response, 2 studies investigating pneumococcal vaccine response). Influenza vaccine responses to all subunit strains (H1N1, H3N2, B strain) were preserved with methotrexate (MTX) and tumor necrosis factor inhibitor (TNFi) drug exposure. MTX but not TNFi drug exposure was associated with reduced 6B and 23F serotype pneumococcal vaccine response (RR 0.42, 95% CI 0.28–0.63 vs RR 0.98, 95% CI 0.58–1.67); however, limited data were available to draw any firm conclusions. Combination of MTX with tocilizumab or tofacitinib was associated with reduced pneumococcal and influenza vaccine responses.Conclusion.Antirheumatic drugs may limit humoral responses to vaccination as evidenced by pneumococcal responses with MTX exposure; however, they are safe and should not preclude immunization against vaccine-preventable disease. Vaccination should be considered in all patients with RA and encouraged as part of routine care. (Systematic review registration number: PROSPERO 2016: CRD42016048093.)
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Bogaert, Debby, Paul van der Valk, Reshmi Ramdin, Marcel Sluijter, Evelyn Monninkhof, Ron Hendrix, Ronald de Groot, and Peter W. M. Hermans. "Host-Pathogen Interaction during Pneumococcal Infection in Patients with Chronic Obstructive Pulmonary Disease." Infection and Immunity 72, no. 2 (February 2004): 818–23. http://dx.doi.org/10.1128/iai.72.2.818-823.2004.
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ABSTRACT Acute exacerbation is a frequent complication of chronic obstructive pulmonary disease (COPD). Recent studies suggested a role for bacteria such as Streptococcus pneumoniae in the development of acute exacerbation. For this study, we investigated the following in COPD patients: (i) the epidemiology of pneumococcal colonization and infection, (ii) the effect of pneumococcal colonization on the development of exacerbation, and (iii) the immunological response against S. pneumoniae. We cultured sputa of 269 COPD patients during a stable state and during exacerbation of COPD and characterized 115 pneumococcal isolates by use of serotyping. Moreover, we studied serum immunoglobulin G (IgG) antibody titers, antibody avidities, and functional antibody titers against the seven conjugate vaccine serotypes in these patients. Colonization with only pneumococci (monocultures) increased the risk of exacerbation, with a hazard ratio of 2.93 (95% confidence interval, 1.41 to 6.07). The most prevalent pneumococcal serotypes found were serotypes 19F, 3, 14, 9L/N/V, 23A/B, and 11. We calculated the theoretical coverage for the 7- and 11-valent pneumococcal vaccines to be 60 and 73%, respectively. All patients had detectable IgG levels against the seven conjugate vaccine serotypes. These antibody titers were significantly lower than those in vaccinated healthy adults. Finally, on average, a 2.5-fold rise in serotype-specific and functional antibodies in S. pneumoniae-positive sputum cultures was observed during exacerbation. Our data indicate that pneumococcal colonization in COPD patients is frequently caused by vaccine serotype strains. Moreover, pneumococcal colonization is a risk factor for exacerbation of COPD. Finally, our findings demonstrate that COPD patients are able to mount a significant immune response to pneumococcal infection. COPD patients may therefore benefit from pneumococcal vaccination.
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Bilgin, Gizem M., Syarifah Liza Munira, Kamalini Lokuge, and Kathryn Glass. "Cost-effectiveness analysis of a maternal pneumococcal vaccine in low-income, high-burden settings such as Sierra Leone." PLOS Global Public Health 3, no. 8 (August 24, 2023): e0000915. http://dx.doi.org/10.1371/journal.pgph.0000915.
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Maternal pneumococcal vaccines have been proposed as a method of protecting infants in the first few months of life. In this paper, we use results from a dynamic transmission model to assess the cost-effectiveness of a maternal pneumococcal polysaccharide vaccine from both healthcare and societal perspectives. We estimate the costs of delivering a maternal pneumococcal polysaccharide vaccine, the healthcare costs averted, and productivity losses avoided through the prevention of severe pneumococcal outcomes such as pneumonia and meningitis. Our model estimates that a maternal pneumococcal program would cost $606 (2020 USD, 95% prediction interval 437 to 779) from a healthcare perspective and $132 (95% prediction interval -1 to 265) from a societal perspective per DALY averted for one year of vaccine delivery. Hence, a maternal pneumococcal vaccine would be cost-effective from a societal perspective but not cost-effective from a healthcare perspective using Sierra Leone’s GDP per capita of $527 as a cost-effectiveness threshold. Sensitivity analysis demonstrates how the choice to discount ongoing health benefits determines whether the maternal pneumococcal vaccine was deemed cost-effective from a healthcare perspective. Without discounting, the cost per DALY averted would be $292 (55% of Sierra Leone’s GDP per capita) from a healthcare perspective. Further, the cost per DALY averted would be $142 (27% GDP per capita) from a healthcare perspective if PPV could be procured at the same cost relative to PCV in Sierra Leone as on the PAHO reference price list. Overall, our paper demonstrates that maternal pneumococcal vaccines have the potential to be cost-effective in low-income settings; however, the likelihood of low-income countries self-financing this intervention will depend on negotiations with vaccine providers on vaccine price. Vaccine price is the largest program cost driving the cost-effectiveness of a future maternal pneumococcal vaccine.