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Journal articles on the topic 'Vaccines Synthesis'
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1
Adegbite, Ayobami, and Pumtiwitt C. McCarthy. "Recent and Future Advances in the Chemoenzymatic Synthesis of Homogeneous Glycans for Bacterial Glycoconjugate Vaccine Development." Vaccines 9, no. 9 (September 14, 2021): 1021. http://dx.doi.org/10.3390/vaccines9091021.
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Vaccines are important in preventing disease outbreaks and controlling the spread of disease in a population. A variety of vaccines exist, including subunit, recombinant, and conjugate vaccines. Glycoconjugate vaccines have been an important tool to fight against diseases caused by a number of bacteria. Glycoconjugate vaccines are often heterogeneous. Vaccines of the future are becoming more rationally designed to have a defined oligosaccharide chain length and position of conjugation. Homogenous vaccines could play an important role in assessing the relationship between vaccine structure and immune response. This review focuses on recent advances in the chemoenzymatic production of defined bacterial oligosaccharides for vaccine development with a focus on Neisseria meningitidis and selected WHO-prioritized antibacterial resistant-pathogens. We also provide some perspective on future advances in the chemoenzymatic synthesis of well-defined oligosaccharides.
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Zhou, Yang, Abid H. Banday, Victor J. Hruby, and Minying Cai. "Development of N-Acetylated Dipalmitoyl-S-Glyceryl Cysteine Analogs as Efficient TLR2/TLR6 Agonists." Molecules 24, no. 19 (September 27, 2019): 3512. http://dx.doi.org/10.3390/molecules24193512.
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Cancer vaccine is a promising immunotherapeutic approach to train the immune system with vaccines to recognize and eliminate tumors. Adjuvants are compounds that are necessary in cancer vaccines to mimic an infection process and amplify immune responses. The Toll-like receptor 2 and 6 (TLR2/TLR6) agonist dipalmitoyl-S-glyceryl cysteine (Pam2Cys) was demonstrated as an ideal candidate for synthetic vaccine adjuvants. However, the synthesis of Pam2Cys requires expensive N-protected cysteine as a key reactant, which greatly limits its application as a synthetic vaccine adjuvant in large-scaled studies. Here, we report the development of N-acetylated Pam2Cys analogs as TLR2/TLR6 agonists. Instead of N-protected cysteine, the synthesis utilizes N-acetylcysteine to bring down the synthetic costs. The N-acetylated Pam2Cys analogs were demonstrated to activate TLR2/TLR6 in vitro. Moreover, molecular docking studies were performed to provide insights into the molecular mechanism of how N-acetylated Pam2Cys analogs bind to TLR2/TLR6. Together, these results suggest N-acetylated Pam2Cys analogs as inexpensive and promising synthetic vaccine adjuvants to accelerate the development of cancer vaccines in the future.
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Goldstein, Leslie GB. "Safety and Efficacy of Influenza Vaccine in Children." Annals of Pharmacotherapy 37, no. 11 (November 2003): 1712–15. http://dx.doi.org/10.1345/aph.1d009.
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OBJECTIVE: To describe the safety and efficacy of influenza vaccines in asthmatic children. DATA SOURCES: Literature was identified by a MEDLINE search (2002–March 2003). Key search terms included asthma, exacerbation, children, vaccine, and influenza. DATA SYNTHESIS: Concerns that the influenza vaccine may exacerbate asthma attacks have kept many asthmatic children from receiving this immunization. Researchers have conducted studies to determine the burden of influenza on asthmatic children, the safety of influenza vaccines, and their benefit in the presence of glucocorticoid burst therapy in the same population. CONCLUSIONS: Influenza vaccines tested are safe and efficacious in asthmatic children.
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Wintermeyer, Susan M., Milap C. Nahata, and Kay S. Kyllonen. "Whole-Cell and Acellular Pertussis Vaccines." Annals of Pharmacotherapy 28, no. 7-8 (July 1994): 925–39. http://dx.doi.org/10.1177/106002809402800718.
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OBJECTIVE: To provide a review of pertussis vaccines, including information on efficacy, adverse reactions, and antibody production following administration of both whole-cell and acellular pertussis vaccines. DATA SOURCES: A MEDLINE search and extensive review of journals was conducted to identify the information for this review. DATA EXTRACTION: Pertinent studies reporting experience with pertussis vaccinations were reviewed. DATA SYNTHESIS: The differences in efficacy, adverse reactions, and antibody responses between whole-cell and acellular pertussis vaccines are emphasized. The status of acellular pertussis vaccination in the US is defined. CONCLUSIONS: Acellular (chemically detoxified or recombinant) pertussis vaccine formulation appears to cause fewer adverse reactions than whole-cell vaccine in most studies. Clinical efficacy and safety in the very young has not been well established. Thus, acellular pertussis vaccine is reserved for the 4th and 5th doses in the US. Oral or intranasal formulations of the pertussis vaccine are being evaluated.
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Mitchell, Hana, Rebecca Lim, Prubjot K. Gill, Joban Dhanoa, Ève Dubé, and Julie A. Bettinger. "What do adolescents think about vaccines? Systematic review of qualitative studies." PLOS Global Public Health 2, no. 9 (September 29, 2022): e0001109. http://dx.doi.org/10.1371/journal.pgph.0001109.
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Adolescence presents a key opportunity to build vaccine-related health literacy and promote vaccine confidence and uptake. Although adolescents are central to vaccination programs, their views around vaccines are frequently underrepresented in qualitative literature. We reviewed qualitative studies to systematically identify and summarize existing evidence on adolescents’ own understanding of vaccines and experiences with vaccine decision-making, including self-consent when applicable. CINAHL; Embase; Ovid Medline; and Psych Info database searches were last updated on May 28, 2022. Data pertaining to general study characteristics, participant demographics, and qualitative content were extracted independently by two reviewers and analyzed using textual narrative synthesis. Out of 3559 individual records, 59 studies were included. The majority of the studies were conducted in high-income countries and 75% focused on human papilloma virus vaccines, with the remaining studies looking at COVID-19, meningococcal, hepatitis B and influenza vaccines or adolescent experiences with vaccines in general. Adolescent self-consent was explored in 7 studies. Perspectives from sexual and gender minorities were lacking across studies. Adolescents often had limited understanding of different vaccines and commonly perceived vaccine information to be directed towards their parents rather than themselves. Many adolescents felt school-based vaccine education and information available through healthcare providers were insufficient to make informed decisions about vaccines. While adolescents described obtaining vaccine information from traditional and online media, face-to-face interactions and opinions from trusted adults remained important. Adolescents generally relied on their parents for vaccine-decision making, even when self-consent was an option. A notable exception to this included marginalized adolescents who could not rely on parents for health-related advice. Qualitative literature about adolescent vaccines would be enriched by studies examining vaccines other than the HPV vaccine, studies examining adolescent vaccine programs in low and middle-income countries, and by deliberately eliciting vaccine experiences of adolescent with diverse sexual orientation and gender identities.
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Xu, Shuqin, Kunpeng Yang, Rose Li, and Lu Zhang. "mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection." International Journal of Molecular Sciences 21, no. 18 (September 9, 2020): 6582. http://dx.doi.org/10.3390/ijms21186582.
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Messenger ribonucleic acid (mRNA)-based drugs, notably mRNA vaccines, have been widely proven as a promising treatment strategy in immune therapeutics. The extraordinary advantages associated with mRNA vaccines, including their high efficacy, a relatively low severity of side effects, and low attainment costs, have enabled them to become prevalent in pre-clinical and clinical trials against various infectious diseases and cancers. Recent technological advancements have alleviated some issues that hinder mRNA vaccine development, such as low efficiency that exist in both gene translation and in vivo deliveries. mRNA immunogenicity can also be greatly adjusted as a result of upgraded technologies. In this review, we have summarized details regarding the optimization of mRNA vaccines, and the underlying biological mechanisms of this form of vaccines. Applications of mRNA vaccines in some infectious diseases and cancers are introduced. It also includes our prospections for mRNA vaccine applications in diseases caused by bacterial pathogens, such as tuberculosis. At the same time, some suggestions for future mRNA vaccine development about storage methods, safety concerns, and personalized vaccine synthesis can be found in the context.
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Force, Rex W., Ralph A. Lugo, and Milap C. Nahata. "Haemophilus Influenzae Type B Conjugate Vaccines." Annals of Pharmacotherapy 26, no. 11 (November 1992): 1429–40. http://dx.doi.org/10.1177/106002809202601117.
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OBJECTIVE: To review the epidemiology of Haemophilus influenzae type b (Hib) disease, the first Hib vaccine and its limitations, the characteristics and clinical efficacy of the newer conjugate vaccines, and the current recommendations for administration of Hib vaccines. DATA SOURCES: Pertinent literature was identified via a MEDLINE search. Additionally, references cited in published articles were used as data sources. STUDY SELECTION: Studies describing the epidemiology of Hib disease and the efficacy and/or immunogenicity of the Hib vaccines are reviewed. DATA SYNTHESIS: Serious invasive disease secondary to Hib infection causes significant morbidity and mortality in children between the ages of three months and five years. The original Hib vaccine was found to be ineffective in stimulating an adequate immune response in children younger than two years of age. The new Hib conjugate vaccines provide superior efficacy and immunogenicity compared with the original unconjugated vaccine. They stimulate an immune response that is distinctly different from that elicited by the original vaccine. Two vaccine products are currently licensed for use in children as young as two months of age, thus conferring immunity to those children at highest risk for Hib disease. CONCLUSIONS: The new Hib conjugate vaccines provide excellent efficacy and, when used as recommended, may significantly reduce the incidence of invasive Hib disease and its sequelae.
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Sheibak, V. M., and M. V. Haretskaya. "DEVELOPMENT OF VACCINES FOR SARS-COV-2." Journal of the Grodno State Medical University 20, no. 1 (March 1, 2022): 5–12. http://dx.doi.org/10.25298/2221-8785-2022-20-1-5-12.
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Background. Currently, an active search for effective vaccines against the SARS-CoV-2 coronavirus continues. Purpose. To analyze the literature and assess the status of active vaccine development against SARS-CoV-2. Material and methods. We analyzed Russian and English language literature sources on the problem of finding an effective vaccine against SARS-CoV-2. Results. Structural proteins of the coronavirus have been analyzed as basic compounds for the development of vaccines. It was found that protein S is an ideal structure for creating vaccines that effectively induce the synthesis of neutralizing antibodies and provide the formation of immunity. Information about current trends in vaccine development has been obtained. Conclusions. The SARS-CoV-2 virus continues to mutate, which leads to the emergence of new highly contagious strains such as Delta, Omicron. In this regard, more research and clinical trials are needed to confirm the effectiveness of the current SARS-CoV-2 vaccines, or to continue developing the new ones.
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Su, Huali, Qing Liu, Xiaoping Bian, Shifeng Wang, Roy Curtiss, and Qingke Kong. "Synthesis and delivery of Streptococcus pneumoniae capsular polysaccharides by recombinant attenuated Salmonella vaccines." Proceedings of the National Academy of Sciences 118, no. 2 (December 30, 2020): e2013350118. http://dx.doi.org/10.1073/pnas.2013350118.
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Streptococcus pneumoniae capsular polysaccharides (CPSs) are major determinants of bacterial pathogenicity. CPSs of different serotypes form the main components of the pneumococcal vaccines Pneumovax, Prevnar7, and Prevnar13, which substantially reduced the S. pneumoniae disease burden in developed countries. However, the laborious production processes of traditional polysaccharide-based vaccines have raised the cost of the vaccines and limited their impact in developing countries. The aim of this study is to develop a kind of low-cost live vaccine based on using the recombinant attenuated Salmonella vaccine (RASV) system to protect against pneumococcal infections. We cloned genes for seven different serotypes of CPSs to be expressed by the RASV strain. Oral immunization of mice with the RASV-CPS strains elicited robust Th1 biased adaptive immune responses. All the CPS-specific antisera mediated opsonophagocytic killing of the corresponding serotype of S. pneumoniae in vitro. The RASV-CPS2 and RASV-CPS3 strains provided efficient protection of mice against challenge infections with either S. pneumoniae strain D39 or WU2. Synthesis and delivery of S. pneumoniae CPSs using the RASV strains provide an innovative strategy for low-cost pneumococcal vaccine development, production, and use.
10
Moysa, A. A., and E. F. Kolesanova. "Synthetic peptide vaccines." Biomeditsinskaya Khimiya 57, no. 1 (January 2011): 14–30. http://dx.doi.org/10.18097/pbmc20115701104.
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This review considers the stages of the development of synthetic peptide vaccines against infectious agents, novel approaches and technologies employed in this process, including bioinformatics, genomics, proteomics, large-scale peptide synthesis, high-throughput screening methods, the use of transgenic animals for modelling human infections. An important role for the development and selection of efficient adjuvants for peptide immunogens is noted. Examples of synthetic peptide vaccine developments against three infectious diseases (malaria, hepatitis C, and foot-and-mouth disease) are given.
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Ilyichev, A. A., L. A. Orlova, S. V. Sharabrin, and L. I. Karpenko. "mRNA technology as one of the promising platforms for the SARS-CoV-2 vaccine development." Vavilov Journal of Genetics and Breeding 24, no. 7 (December 6, 2020): 802–7. http://dx.doi.org/10.18699/vj20.676.
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After the genome sequence of SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus 2) was published and the number of infected people began to increase rapidly, many global companies began to develop a vaccine. Almost all known approaches to vaccine design were applied for this purpose, including inactivated viruses, mRNA and DNA-vaccines, vaccines based on various viral vectors, synthetically generated peptides and recombinant proteins produced in cells of insects and mammals. This review considers one of the promising vaccine platforms based on messenger RNA. Until recent years, mRNA-vaccination was out of practical implementation due to high sensitivity to nuclease degradation and consequent instability of drugs based on mRNA. Latest technological advances significantly mitigated the problems of low immunogenicity, instability, and difficulties in RNA-vaccine delivery. It is worth noting that mRNA-vaccines can efficiently activate both components of the immune system, i. e. T-cell and humoral responses. The essential advantage of mRNA-vaccines includes fast, inexpensive, scalable and uniform production providing a large output of desirable products in vitro. Synthesis and purification processes significantly simplify the process technology of mRNA drugs with injectable purity. Thus, mRNA production via in vitro transcription is more advantageous as compared with DNA-vaccines since it is a chemical process without the use of cells. mRNA techniques make it possible to pass all the phases of vaccine development much faster in comparison with the production of vaccines based on inactivated viruses or recombinant proteins. This property is critically important when designing vaccines against viral pathogens as the main problem of disease control includes a time gap between an epidemic and vaccine development. This paper discusses studies on the development of vaccines against coronaviruses including SARS-CoV-2 with special attention to the mRNA technique.
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Wei, Jiao, and Aimin Hui. "Review of Ribosome Interactions with SARS-CoV-2 and COVID-19 mRNA Vaccine." Life 12, no. 1 (January 1, 2022): 57. http://dx.doi.org/10.3390/life12010057.
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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causing pathogen of the unprecedented global Coronavirus Disease 19 (COVID-19) pandemic. Upon infection, the virus manipulates host cellular machinery and ribosomes to synthesize its own proteins for successful replication and to facilitate further infection. SARS-CoV-2 executes a multi-faceted hijacking of the host mRNA translation and cellular protein synthesis. Viral nonstructural proteins (NSPs) interact with a range of different ribosomal states and interfere with mRNA translation. Concurrent mutations on NSPs and spike proteins contribute to the epidemiological success of variants of concern (VOCs). The interactions between ribosomes and SARS-CoV-2 represent attractive targets for the development of antiviral therapeutics and vaccines. Recently approved COVID-19 mRNA vaccines also utilize the cellular machinery, to produce antigens and trigger immune responses. The design features of the mRNA vaccines are critical to efficient mRNA translation in ribosomes, and are directly related to the vaccine’s efficacy, safety, and immunogenicity. This review describes recent knowledge of how the SARS-CoV-2 virus’ genomic characteristics interfere with ribosomal function and mRNA translation. In addition, we discuss the current learning of the design features of mRNA vaccines and their impacts on translational activity in ribosomes. The understanding of ribosomal interactions with the virus and mRNA vaccines offers the foundation for antiviral therapeutic discovery and continuous mRNA vaccine optimization to lower the dose, to increase durability and/or to reduce adverse effects.
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Ramachandran, Suryanarayan, and Philip K. Russell. "Conclusion: A New Technologic Synthesis: The Children's Vaccine Initiative." International Journal of Technology Assessment in Health Care 10, no. 1 (1994): 193–96. http://dx.doi.org/10.1017/s0266462300014124.
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If the visionary goals of the Children's Vaccine Initiative (CVI) are to be achieved, it will have to be an initiating, integrating, and propelling force in the development, manufacturing, and use of vaccines. Success in solving the major technological challenges may depend first on solving the problem of incorporating the major players into the CVI. Today's relationship between private vaccine manufacturers and publicsector purchasers must give way to a new era of cooperation and coordination.
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Hossain, Farzana, Shruthi Kandalai, Xiaozhuang Zhou, Nan Zhang, and Qingfei Zheng. "Chemical and Synthetic Biology Approaches for Cancer Vaccine Development." Molecules 27, no. 20 (October 16, 2022): 6933. http://dx.doi.org/10.3390/molecules27206933.
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Cancer vaccines have been considered promising therapeutic strategies and are often constructed from whole cells, attenuated pathogens, carbohydrates, peptides, nucleic acids, etc. However, the use of whole organisms or pathogens can elicit unwanted immune responses arising from unforeseen reactions to the vaccine components. On the other hand, synthetic vaccines, which contain antigens that are conjugated, often with carrier proteins, can overcome these issues. Therefore, in this review we have highlighted the synthetic approaches and discussed several bioconjugation strategies for developing antigen-based cancer vaccines. In addition, the major synthetic biology approaches that were used to develop genetically modified cancer vaccines and their progress in clinical research are summarized here. Furthermore, to boost the immune responses of any vaccines, the addition of suitable adjuvants and a proper delivery system are essential. Hence, this review also mentions the synthesis of adjuvants and utilization of biomaterial scaffolds, which may facilitate the design of future cancer vaccines.
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Starostina, E. V., S. V. Sharabrin, A. P. Rudometov, V. R. Litvinova, M. B. Borgoyakova, S. I. Bazhan, A. A. Ilyichev, and L. I. Karpenko. "Immune response against DNA- and mRNA vaccines encoding artificial influenza virus immunogens." Russian Journal of Immunology 25, no. 3 (September 20, 2022): 321–26. http://dx.doi.org/10.46235/1028-7221-1103-ira.
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Constant antigenic drift of circulating influenza viruses leads to inefficiency of seasonal influenza vaccines, thus requiring annual re-design of these vaccines. Therefore, the development of a universal influenza vaccine is of particular relevance. A promising line of research in this area is to design the immunogens consisting of conserved protein fragments from different influenza viral strains. The aim of this work was to assess immunogenicity of DNA vaccines and mRNA vaccines encoding artificial antigens consisting of conserved hemagglutinin stem fragments and conserved M2 protein. We have obtained DNA vaccine constructs encoding artificial immunogens AgH1, AgH3, and AgM2, which contained conserved fragments of the hemagglutinin stalk from the two subtypes of influenza A H1N1 and H3N2, and conserved M2 protein. These DNA vaccines were used as templates for the synthesis of mRNA vaccines. To assess immunogenicity of the obtained constructs, BALB/c mice were immunized with DNA and mRNA vaccines by i/m administration. Assessment of the humoral immune response was carried out by ELISA, using influenza viruses A/Aichi/2/68(H3N2), A/California/07/2009 as antigens and the ULTRIX vaccine containing purified antigens of H1N1 and H3N2 influenza viruses. T cell immune response was assessed using two methods: intracellular cytokine staining (ICS) and ELISpot. ICS was performed to determine CD8+ and CD4+T-lymphocytes producing IFN. ELISpot was carried out using the mouse IFN ELISpot kit (BD). A peptide mixture which included composition of the target antigens, was used for cell stimulation. The results showed that the designed DNA vaccine constructs induce virus-specific humoral and cellular responses in immunized BALB/c mice. Intramuscular administration of the naked mRNA vaccine constructs induced a weak humoral immune response, thus suggesting a need for further work to improve the delivery approaches.
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van den Berg, Jesse M., Sharon Remmelzwaal, Marieke T. Blom, Beryl A. C. E. van Hoek, Karin M. A. Swart, Jetty A. Overbeek, George L. Burchell, Ron M. C. Herings, and Petra J. M. Elders. "Effectiveness of COVID-19 Vaccines in Adults with Diabetes Mellitus: A Systematic Review." Vaccines 11, no. 1 (December 22, 2022): 24. http://dx.doi.org/10.3390/vaccines11010024.
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Persons with diabetes mellitus may have an increased risk of severe illness or death from COVID-19 compared to persons without diabetes. Prior studies indicate that immune response and thus vaccine effectiveness might be lower in persons with diabetes. We aimed to systematically review the effectiveness of COVID-19 vaccines in adults with diabetes. Pubmed, Embase, Web of Science and Cochrane Library were searched for studies that evaluated the effectiveness of COVID-19 vaccines in adults with diabetes, published before 4 March 2022. Risk of bias in the included studies was evaluated using the ROBINS-I tool. At least two reviewers conducted the study selection, data extraction, and risk of bias assessment independently. After screening of 2196 studies, a total of 17 articles were included. Six different COVID-19 vaccines (Ad5-nCoV-S, AZD1222, BNT162b2, CoronaVac, JNJ-78436735, and mRNA-1273) were included in the synthesis. Vaccine effectiveness was reported for SARS-CoV-2 infection, symptomatic COVID-19, hospitalization, and death, and ranged from 24 to 96% in persons with diabetes, and from 33 to 97% in total study populations; effectiveness was generally lower for persons with diabetes. Odds ratios for breakthrough infection or severe COVID-19 ranged from 1.03 to 2.41 in vaccinated persons with diabetes compared to persons without diabetes. Even though the included studies were very heterogeneous, results from the synthesis indicate that effectiveness of COVID-19 vaccines might be lower in persons with diabetes. More research is needed on the comparison of vaccine effectiveness between persons with and without diabetes, and the effectiveness of repeat COVID-19 vaccinations.
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Zhong, Wei, Mariusz Skwarczynski, Yoshio Fujita, Pavla Simerska, Michael F. Good, and Istvan Toth. "Design and Synthesis of Lipopeptide - Carbohydrate Assembled Multivalent Vaccine Candidates Using Native Chemical Ligation." Australian Journal of Chemistry 62, no. 9 (2009): 993. http://dx.doi.org/10.1071/ch09065.
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Development of a synthetic vaccine against group A streptococcal infection is increasingly paramount due to the induction of autoimmunity by the main virulent factor – M protein. Peptide vaccines, however, are generally poorly immunogenic, necessitating administration with carriers and adjuvants. One of the promising approaches to deliver antigenic peptides is to assemble peptides on a suitable template which directs the attached peptides to form a well defined tertiary structure. For self-adjuvanting human vaccines, the conjugation of immunostimulatory lipids has been demonstrated as a potentially safe method. This study describes the design and optimized synthesis of two lipopeptide conjugated carbohydrate templates and the assembling of peptide antigens. These lipopeptide–carbohydrate assembled multivalent vaccine candidates were obtained in high yield and purity when native chemical ligation was applied. Circular dichroism studies indicated that the template-assembled peptides form four α-helix bundles. The developed technique extends the use of carbohydrate templates and lipopeptide conjugates for producing self-adjuvanting and topology-controlled vaccine candidates.
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Thompson, Paul Wesley. "Efficacy of Covid-19 Vaccines in Ethnically Diverse Population (BAME): A Systematic Review." Pakistan Journal of Medical and Health Sciences 16, no. 7 (July 30, 2022): 922–25. http://dx.doi.org/10.53350/pjmhs22167922.
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Background: The Black, Asian, and minority ethnic (BAME) groups are more prone to covid-19 disease severity and its associated mortality. The research has reported that the response of vaccines against different viral infections has varied among different groups of populations such as age, gender, race, and comorbidities. Therefore, the present study aimed to evaluate the efficacy of covid-19 vaccines of Emergency Use License (EUL) in BAME ethnicities. Method: We conducted a systematic review by using different names of EUL vaccines in Cochrane Covid-19 Study Register (CCSR) and WHO Covid‐19 global literature and exported the retrieved results to EndNote X8 to eliminate the duplicate records. The study followed PRISMA (Preferred Items for Reporting Systematic Reviews and Meta-analysis) guidelines for reporting systematic reviews. We descriptively reviewed the included studies and performed data synthesis for randomized controlled trials (RCTs). Results: A total of 4799 retrieved records were filtered down to 13 studies for inclusion which comprised nine RCTs, three case-control studies, and one retrospective cohort. The RCTs included in the data synthesis covered mRNA-1273, BNT162b2, NVX-CoV2373, AZD1222, and Ad26.COV2.S vaccines and reported 603 total events out of 125,874 participants in the interventional group and 3115 total events out of 109,093 participants in placebo groups. Compared to White participants, one RCT showed higher efficacy of mRNA-1237 in communities of color, whereas another RCT showed higher efficacy in Asians. Two RCTs showed that BNT162b2 had the highest efficacy (100%) in Black ethnicity. Similarly, one RCT of each NVX-CoV2373 and AZD1222 reported the highest efficacies of the respective vaccine in Black individuals. Among different vaccines, the Asian obtained the highest efficacy with mRNA-1273 but the lowest with BNT162b2. However, the data synthesis revealed a statistically significant favor for the efficacy of all vaccines over placebo across all subgroups of ethnicities. Conclusion: The covid-19 vaccines have non-inferior efficacy in different ethnicities. Nonetheless, the mRNA vaccines might be comparatively suitable for Black and Asian individuals in terms of efficacy than other vaccines. However, more studies with substantial representation of the BAME population are warranted to increase the magnitude of evidence in this regard. Keywords: Covid-19, vaccines, efficacy, BAME
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Grabenstein, John D. "Should Vaccines Require a Prescription?" Annals of Pharmacotherapy 32, no. 4 (April 1998): 495–500. http://dx.doi.org/10.1345/aph.17313.
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OBJECTIVE: To review the rationale for requiring prescriptions to control vaccine access, in contrast to other medications. DATA SOURCES: Literature on immunization delivery and health-service barriers was reviewed via MEDLINE search and relevant textbooks. Additional literature was obtained from reference lists of pertinent articles. DATA SYNTHESIS: Society controls access to medications to protect consumers. Many medications have changed from prescription-only to over-the-counter (OTC) status. No parenteral drug has been switched, although insulin has long had OTC status. Limiting access to vaccines has advantages in record-keeping, storage, injection quality, and response to anaphylactic reactions. These advantages are outweighed by 600 000 people who will die over the next decade for lack of pneumococcal and influenza immunizations. Physicians see most of those who die of these diseases, but many neglect to vaccinate them. Three options are offered to expand access to these vaccines. The most feasible one involves expanding prescribing authority for pneumococcal and influenza vaccines to all licensed healthcare professionals and paraprofessionals with physiologic and pharmacologic expertise to responsibly vaccinate. Community pharmacies offer advantages as immunization delivery sites, in terms of proximity, hours of operation, and knowledge of people at highest risk. Expanded professional training can ensure high levels of public safeguards while expanding immunization delivery. CONCLUSIONS: Society decides the controls needed to protect the health of the people. If society restricts vaccine access too severely, people die needlessly. Increasing prescribing authority for pneumococcal and influenza vaccines to more health professionals will save many lives. OBJETIVO: Discutir argumentos a favor y en contra de requerir una receta como método de control de acceso a las vacunas. FUENTES DE INFORMACIÓN: Se realizó una búsqueda bibliográfica en MEDLINE y se revisaron libros de texto para obtener literatura relacionada a la inmunización y las barreras para obtener servicios de salud. Se obtuvo literatura adicional de las listas de referencias de manuscritos relacionados al tema. SÍNTESIS: La sociedad controla el acceso a medicamentos con el propósito de proteger a los consumidores. Muchos medicamentos que anteriormente sólo se podían obtener con receta médica shora se pueden obtener sin receta. Ningún medicamento que se administra por la vía parenteral se puede obtener sin receta con excepción de la insulina. Limitar el acceso a las vacunas tiene como ventajas un mayor control sobre el mantenimiento de expedientes, el almacenaje, la calidad del producto, y la respuesta a reacciones anafilácticas. Por otro lado, 600 000 personas morirán en la próxima década por no haber recibido inmunización contra neumococos y la influenza. Los proveedores de servicios de salud ven a muchos de los pacientes que mueren como consecuencia de estas enfermedades, pero muchos se niegan a vacunarlos. Se ofrecen tres opciones para expandir el acceso a estas vacunas: (1) otorgar autoridad de prescribir las vacunas a otros profesionales de la salud, (2) autorizar la venta de vacunas sin receta pero únicamente si son dispensadas y administradas por un farmacéutico con adiestramiento, y (3) autorizar la venta de las vacunas sin receta y confiar que el mercado limite su distribución únicamente en farmacias, tal como ocurre con insulina. La opción más viable tiene que ver con otorgar autoridad de prescribir vacunas contra neumococos e influenza a todos los profesionales y para-profesionales de la salud con conocimiento fisiológico y farmacológico suficiente para responsablemente vacunar. Las farmacias de comunidad ofrecen ventajas como lugares donde se podría vacunar a las personas en términos de proximidad, horario de operación, y conocimiento de las personas en alto riesgo. Para salvaguardar la seguridad pública ante la expansión en los servicios de inmunización es necesario asegurar que los ofrecimientos de adiestramiento profesional serán ampliados. CONCLUSIONES: La sociedad decide los controles necesarios para proteger la salud de las personas. Si la sociedad limita el acceso a las vacunas, algunas personas morirán innecesariamente. El aumentar la autoridad para prescribir vacunas contra neumococos y la influenza a un mayor número de profesionales de la salud salvará muchas vidas. OBJECTIF: Examiner la nécessité d'obtenir les prescriptions afin de contrôler l'accès aux vaccins contrairement à d'autres médicaments. REVUE DE LITTÉRATURE: La documentation scientifique concernant la distribution des vaccins et les normes du réseau de la santé ont été revisées à l'aide d'une recherche informatisée MEDLINE et de livres de références sur le sujet. De la documentation additionnelle a été obtenue des bibliographies provenants de manuscrits pertinents. RÉSUMÉ: La société contrôle l'accès aux médicaments dans le but de protèger le public. Plusieurs médicaments sont passés du statut de médicaments prescrits à celui de médicaments de vente libre (MVL). Aucun produit parentérale n'a changé de statut, quoique l'insuline a depuis longtemps un statut de MVL. L'accès limité aux vaccins facilite la tenue de livres, les conditions d'entreposage, la qualité de l'injection et la réponse à des réactions anaphylactiques. Ces avantages s'opposent cependant au fait que 600 000 individus mourront dans la prochaine décennie par manque d'immunisation contre le pneumocoque ou l'influenza. Les médecins voient la majorité de ces patients qui décéderont suite à ces troubles, mais plusieurs négligent de les vacciner. Trois options sont offertes pour accroître l'accès à ces vaccins. L'option la plus praticable implique d'élargir l'autorité en matière de prescriptions pour les vaccins contre le pneumocoque et l'influenza à tous les professionnels et paraprofessionnels licenciés de la santé avec expérience physiologique et pharmacologique afin de vacciner de façon responsable. Les pharmacies communautaires offrent des avantages comme sites de distribution des vaccins en terme de proximité, heures d'ouverture et connaissance des patients à risques plus élevés. Une formation plus étendue des professionnels peut assurer une protection accrue du public tout en élargissant la distribution des vaccins. CONCLUSIONS: La société décide des contrôles nécessaires à la protection de la santé du public. Si la société restreint l'accès aux vaccins trop sévèrement, des gens décèdent inutilement. Accroître l'autorité de prescrire les vaccins contre le pneumocoque et l'influenza à plus de professionnels de la santé pourrait sauver des vies.
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Zeigler, David F., Emily Gage, and Christopher H. Clegg. "Epitope-targeting platform for broadly protective influenza vaccines." PLOS ONE 16, no. 5 (May 27, 2021): e0252170. http://dx.doi.org/10.1371/journal.pone.0252170.
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Seasonal influenza vaccines are often ineffective because they elicit strain-specific antibody responses to mutation-prone sites on the hemagglutinin (HA) head. Vaccines that provide long-lasting immunity to conserved epitopes are needed. Recently, we reported a nanoparticle-based vaccine platform produced by solid-phase peptide synthesis (SPPS) for targeting linear and helical protein-based epitopes. Here, we illustrate its potential for building broadly protective influenza vaccines. Targeting known epitopes in the HA stem, neuraminidase (NA) active site, and M2 ectodomain (M2e) conferred 50–75% survival against 5LD50 influenza B and H1N1 challenge; combining stem and M2e antigens increased survival to 90%. Additionally, protein sequence and structural information were employed in tandem to identify alternative epitopes that stimulate greater protection; we report three novel HA and NA sites that are highly conserved in type B viruses. One new target in the HA stem stimulated 100% survival, highlighting the value of this simple epitope discovery strategy. A candidate influenza B vaccine targeting two adjacent HA stem sites led to >104-fold reduction in pulmonary viral load. These studies describe a compelling platform for building vaccines that target conserved influenza epitopes.
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de Clavijo, Irene V., and C. Wayne Weart. "Update on Childhood Immunizations." Annals of Pharmacotherapy 28, no. 5 (May 1994): 633–42. http://dx.doi.org/10.1177/106002809402800514.
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OBJECTIVE: To provide an overview of childhood immunizations with emphasis in new recommendations, as well as recent vaccine developments and special populations. DATA SOURCES: English language literature identified via a MEDLINE search. Additional references were obtained from cited references. STUDY SELECTION AND DATA EXTRACTION: Original articles, reviews, and official publications were used to obtain the most accurate data on safety and efficacy of available pediatric vaccines, as well as current recommendations for their use. DATA SYNTHESIS: Immunizations have been an area of vigorous research for several years. New vaccines have been developed by improving older products to maximize immunogenicity and minimize adverse effects. Some of these novel vaccines, like the Haemophilus influenzae type b conjugate vaccines (HibCV), have already contributed significantly to the prevention of diseases in childhood. New recommendations have been issued to help speed this process. Adverse effects of routine immunizations are generally mild and transient. CONCLUSIONS: The development of new effective and safe vaccines for children is an important step in the global eradication of contagious diseases. A new generation of combination vaccines has started with the combination of the diphtheria-tetanus-pertussis vaccine and HibCV. Some other combined products are yet to come that would eventually make immunization schedules more costeffective and improve compliance rates. Our colleagues in the community and in the ambulatory care setting must actively participate in the implementation of vaccination programs and provide education to parents regarding all aspects of the immunization process.
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Meuleman, Theodorus J., Vanessa M. Cowton, Arvind H. Patel, and Rob M. J. Liskamp. "Design and Synthesis of HCV-E2 Glycoprotein Epitope Mimics in Molecular Construction of Potential Synthetic Vaccines." Viruses 13, no. 2 (February 20, 2021): 326. http://dx.doi.org/10.3390/v13020326.
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Hepatitis C virus remains a global threat, despite the availability of highly effective direct-acting antiviral (DAA) drugs. With thousands of new infections annually, the need for a prophylactic vaccine is evident. However, traditional vaccine design has been unable to provide effective vaccines so far. Therefore, alternative strategies need to be investigated. In this work, a chemistry-based approach is explored towards fully synthetic peptide-based vaccines using epitope mimicry, by focusing on highly effective and conserved amino acid sequences in HCV, which, upon antibody binding, inhibit its bio-activity. Continuous and discontinuous epitope mimics were both chemically synthesized based on the HCV-E2 glycoprotein while using designed fully synthetic cyclic peptides. These cyclic epitope mimics were assembled on an orthogonally protected scaffold. The scaffolded epitope mimics have been assessed in immunization experiments to investigate the elicitation of anti-HCV-E2 glycoprotein antibodies. The neutralizing potential of the elicited antibodies was investigated, representing a first step in employing chemically synthesized epitope mimics as a novel strategy towards vaccine design.
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Hale, Katherine S., and Sherrill J. Brown. "Licensed Vaccines for Rotavirus Prevention in the US: A Review." Journal of Pharmacy Technology 25, no. 5 (September 2009): 309–22. http://dx.doi.org/10.1177/875512250902500506.
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Objective: To review the pharmacology, efficacy, safety, and tolerability of RotaTeq and RotaRix, 2 rotavirus vaccines. Data Sources: English-language articles were obtained via MEDLINE (1966-August 2009) and EMBASE (1980-August 2009) searches using the key words rotavirus vaccine, epidemiology, diarrhea, intussusception, RotaShield, RotaTeq, and RotaRix. Bibliographies of selected articles were used to identify additional sources. Study Selection and Data Extraction: Available published articles reporting the results of human studies of rotavirus vaccines were reviewed for inclusion in this article. Additional information regarding clinical trials and adverse events was obtained from the manufacturer's prescribing information for each vaccine. Data Synthesis: RotaTeq is a live, attenuated human-bovine pentavalent vaccine, and RotaRix is a live, attenuated human vaccine. Both vaccines are approved for the prevention of rotavirus infection and recommended for routine immunization in healthy infants aged 14 weeks to 8 months. The vaccines differ in virologic characteristics, but clinical trials indicate similar efficacy and safety. Each vaccine is more than 70% effective in preventing any severity of rotavirus gastroenteritis and more than 98% effective in preventing severe disease through one full season of rotavirus exposure postvaccination. Efficacy begins to wane during the second season of rotavirus exposure. Post hoc analyses of clinical trials indicated an 85–100% reduction in hospitalizations and emergency department visits following vaccination. Both vaccines have been well tolerated. Fever, vomiting, and diarrhea are the most reported adverse events. Intussusception and Kawasaki syndrome have been reported, but occurrence of these events has not been shown to be significant in comparison with the background rate for each adverse event. Conclusions: RotaTeq and RotaRix are effective for the prevention of rotavirus infection in the US, Europe, and Latin America. Additional studies are needed to assess their duration of protection, worldwide efficacy, effect on the reduction of healthcare resource utilization, and adverse event monitoring.
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Mir, Iqra, Sania Aamir, Syed Rizwan Hussain Shah, Muhammad Shahid, Iram Amin, Samia Afzal, Amjad Nawaz, Muhammad Umer Khan, and Muhammad Idrees. "Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic." Osong Public Health and Research Perspectives 13, no. 2 (April 30, 2022): 84–100. http://dx.doi.org/10.24171/j.phrp.2022.0024.
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The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNA-based vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.
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Pozniak, Oksana, Valentina Khmylievska, and Marie Jeanne Ishimwe. "Losses in Pharmaceutical Supply Chains: challenges in efficient vaccine distribution and utilization." Electronic Scientific Journal Intellectualization of Logistics and Supply Chain Management #1 2020 9 (October 2021): 20–30. http://dx.doi.org/10.46783/smart-scm/2021-9-2.
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The article is devoted to the research the problems that arise in pharmaceutical vaccine supply chains. Slow vaccination leads to global economic losses, and the lack of free access to vaccines in many developing countries is a problem not so much in the economic category as in the cost of human life category, which is confirmed by the research of the International Monetary Fund (IMF) and the United Nations (UN). Pharmaceutical vaccine supply chains are subject to special organization and flow management requirements to avoid waste. In the context of the Covid-19 pandemic, bottlenecks inevitably arise that lead to economic, social, human losses, potential and real losses of vaccines and an increasing pressure on reverse logistics. The main bottlenecks at each stage of the supply chain have been identified, which indicate a shift in the main problems in the pharmaceutical supply chain to the distribution and last mile logistics. A detailed analysis of the vaccine distribution system in the city of Kiev was carried out with the help of sites that cover information on used vaccines and losses based on the types of vaccination points of different forms of ownership. Vaccination sites were ranked according to the degree of effective use of vaccines. As a result, the problems of insufficient information support of the vaccination campaign by government agencies were identified, which leads to the loss of vaccines. The role of the state in solving these problems was assumed by public organizations. To accomplish these tasks, an interactive vaccination map was launched, which makes it possible to find the nearest vaccination point, see how many vaccinations were given in a particular medical institution and how many vaccine doses were potentially lost. For the study, empirical research, data analysis and synthesis, expert assessments and generalization methods were used. Calculated the amount of real and potential monetary losses from vaccines that have been disposed of. Recommendations on the use of innovative tools such as Blockchain to prevent potential and manage existing problems in pharmaceutical vaccine supply chains were provided.
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Dmitrieva, M. V., M. A. Baryshnikovа, O. L. Orlova, and V. S. Kosorukov. "Technological aspects of creating neopeptide vaccines." Russian Journal of Biotherapy 21, no. 4 (December 10, 2022): 10–21. http://dx.doi.org/10.17650/1726-9784-2022-21-4-10-21.
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Personalized neoantigen vaccines are a group of individually designed cancer vaccines that enhance patients’ own antigen-specific immune responses. These include vaccines based on dendritic cells, DNA, mRNA and synthetic peptides. An analysis of 98 clinical trials of neoantigenic vaccines from the ClinicalTrials.gov database found that peptide vaccines are one of the most popular cancer vaccines, accounting for about 50 % of clinical trials. They usually consist of a mixture of long or short peptides, dissolved depending on their properties in an appropriate solvent, and an adjuvant that stabilizes and increases their effectiveness. The most used immunoadjuvants in the formulation of neopeptide vaccines are Toll-like receptor agonists (poly-ICLC) and granulocyte-macrophage colony-stimulating factor. The development of neoantigenic vaccines presents a number of distinctive challenges compared to other types of vaccines. The process should cover and validate the various steps in the development, production and administration processes in order to maximize the efficacy and safety of vaccines. In the technology for the production of peptide vaccines, 3 main stages can be distinguished: 1) screening and identification of neoepitopes using the approaches of computer prediction, co-immunoprecipitation, mass spectrometry and cytotoxic experiments; 2) synthesis of peptides by methods of standard solid-phase synthetic peptide chemistry; 3) actually obtaining a vaccine preparation suitable for storage, transportation and administration to the patient. Taking into account the specificity of the drug, the manufacturing process must be carried out strictly according to the Good Manufacturing Practice standard with mandatory quality control of intermediate and finished products
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Johannes, Manuel, Maximilian Reindl, Bastian Gerlitzki, Edgar Schmitt, and Anja Hoffmann-Röder. "Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope." Beilstein Journal of Organic Chemistry 11 (January 23, 2015): 155–61. http://dx.doi.org/10.3762/bjoc.11.15.
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The development of selective anticancer vaccines that provide enhanced protection against tumor recurrence and metastasis has been the subject of intense research in the scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4’F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells.
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Arrowood, Jodi R., and Mary S. Hayney. "Immunization Recommendations for Adults with Cancer." Annals of Pharmacotherapy 36, no. 7-8 (July 2002): 1219–29. http://dx.doi.org/10.1345/aph.1a277.
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OBJECTIVE: To review the published literature on immunizing nonbone marrow transplant adult cancer patients, summarize the findings, and make recommendations for the use of vaccines in this population. DATA SOURCE: A search of MEDLINE and CancerLit was conducted (1966–June 2001) to find English-language clinical studies and review articles pertaining to immunization, vaccines, and cancer in humans. Recommendations of the Advisory Committee on Immunization Practices were used extensively. References of each identified article were subsequently reviewed for additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: Representative epidemiologic reports, clinical trials, and recommendations of expert panels are summarized in this report. Relevant information was selected to describe the epidemiology of vaccine-preventable diseases, efficacy of the vaccines, and recommendations specific to adults with cancer. DATA SYNTHESIS: In general, adults with cancer are at least at the same risk of infection with vaccine-preventable diseases as are healthy populations. Because of their compromised immune function, many patients who have undergone cancer treatment are specifically at increased risk of morbidity and mortality associated with measles and varicella infections. Asplenic patients with lymphoma are at increased risk of fulminant bacterial infections. Influenza infection is associated with significant morbidity in cancer patients. Although the protection conferred by immunization is lower in immunosuppressed patients with cancer, immunization with inactivated vaccines is indicated. Live vaccines should not be used except in very rare instances. CONCLUSIONS: Immunization of adults with cancer is a critical component of their care. Although additional research is necessary, following established recommendations may protect individuals with malignancies from significant morbidity and mortality associated with vaccine-preventable diseases.
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Petrini, Stefano, Carmen Iscaro, and Cecilia Righi. "Antibody Responses to Bovine Alphaherpesvirus 1 (BoHV-1) in Passively Immunized Calves." Viruses 11, no. 1 (January 2, 2019): 23. http://dx.doi.org/10.3390/v11010023.
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To date, in countries where infectious bovine rhinotracheitis (IBR) is widespread, its control is associated with deleted marker vaccines. These products lack one or more genes responsible for the synthesis of glycoproteins or enzymes. In Europe, the most widely used marker vaccine is one in which glycoprotein E (gE−) is deleted, and it is marketed in a killed or modified-live form. Using this type of immunization, it is possible to differentiate vaccinated animals (gE−) from those infected or injected with non-deleted (gE+) products using diagnostic tests specific for gE. The disadvantage of using modified-live gE-products is that they may remain latent in immunized animals and be reactivated or excreted following an immunosuppressive stimulus. For this reason, in the last few years, a new marker vaccine became commercially available containing a double deletion related to genes coding for gE and the synthesis of the thymidine-kinase (tk) enzyme, the latter being associated with the reduction of the neurotropism, latency, and reactivation of the vaccine virus. Intramuscularly and intranasally administered marker products induce a humoral immune response; however, the mother-to-calf antibody kinetics after vaccination with marker vaccines is poorly understood. This review discusses several published articles on this topic.
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Kravchenko, L. M., K. V. Kudzin, and U. A. Prakulevich. "Design of genetic construction for creation DNA vaccine against porcine reproductive and respiratory syndrome." Proceedings of the National Academy of Sciences of Belarus, Biological Series 63, no. 4 (October 30, 2018): 419–25. http://dx.doi.org/10.29235/1029-8940-2018-63-4-419-425.
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The porcine reproductive and respiratory syndrome (PRRS) caused the serious economic damage to swine breeding around the world. It is a viral infective disease against which live attenuated and inactivated vaccines are not always successful. Development of new types of drugs such as DNA vaccines is necessary for improving the protection against the virus. DNA vaccines induce the development of both a cellular and humoral immune response. Such vaccines consist of a plasmid or viral vector with genes of potentially immunogenic proteins. The expression of these genes realized in cells of the vaccinated animal. It leads to the synthesis of antigen proteins triggering the immune response. The purpose of this work is to create a genetic construction that can be used as DNA vaccine against PRRS virus. The construction consists of the commercial vector pVAX1 and open reading frame of two structural proteins of PRRS virus, a lysosomal localization signal sequence of the invariant chain gene and regulatory elements necessary for the expression of cloned genes in mammalian cells.
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Castro, Aaron, Evelyna Derhovanessian, Ulrich Luxemburger, Michaela Beck, Franziska Gehring, Holger Wenschuh, Johannes Zerweck, Florian Kern, Ulf Reimer, and Ugur Sahin. "A Fast, Flexible and Low Cost Process for Neo-Epitope Based Immune Monitoring." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 213.5. http://dx.doi.org/10.4049/jimmunol.198.supp.213.5.
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Abstract Advances in genomic technologies have paved the way to developing personalized cancer vaccines targeting neo-antigens. Patient-specific vaccines, targeting several neo-antigens in one go have already entered the clinic. Such personalized, multi-target approach poses a challenge for immune monitoring of vaccine-specific T-cell responses in a fast, flexible and cost-effective fashion. Most immune monitoring protocols use 9–15-mer synthetic peptides originating from the vaccine target antigen. In contrast to detection of shared antigen-specific T-cells, for which the same peptide batch can be used for several patients, immune monitoring of individual neo-antigen-specific T-cell responses requires small amounts of large numbers of peptides (e.g. 40 × 15-mer peptides for 10 neo-epitopes of 27 amino-acids), which can only be used for one single patient. Therefore, standard peptide synthesis approaches applying commercial peptide synthesizers not only lack required throughput and speed but also generate peptides at prohibitive costs. Here, we present data demonstrating the flexible application of our high-throughput, low cost FastTrack peptide synthesis approach in comparison with different specifications of standard peptides in ex-vivo ELISPOT to monitor neo-antigen specific immune responses in patients participating in the IVAC MUTANOME Phase I clinical trial (NCT02035956). Application of the new peptide synthesis method enables the assembly of up to 1200 peptides in less than 3 weeks at appr. 20% of standard synthesis costs.
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Parameswarappa, Sharavathi G., Claney L. Pereira, and Peter H. Seeberger. "Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens." Beilstein Journal of Organic Chemistry 16 (July 15, 2020): 1693–99. http://dx.doi.org/10.3762/bjoc.16.140.
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Streptococcus pneumoniae (SP) bacteria cause serious invasive diseases. SP bacteria are covered by a capsular polysaccharide (CPS) that is a virulence factor and the basis for SP polysaccharide and glycoconjugate vaccines. The serotype 9V is part of the currently marketed conjugate vaccine and contains an acetate modification. To better understand the importance of glycan modifications in general and acetylation in particular, defined oligosaccharide antigens are needed for serological and immunological studies. Here, we demonstrate a convergent [2 + 3] synthetic strategy to prepare the pentasaccharide repeating unit of 9V with and without an acetate group at the C-6 position of mannosamine.
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Tsvetkov, Yury E., Marina L. Gening, Ekaterina A. Kurbatova, Nelly K. Akhmatova, and Nikolay E. Nifantiev. "Oligosaccharide ligand tuning in design of third generation carbohydrate pneumococcal vaccines." Pure and Applied Chemistry 89, no. 10 (September 26, 2017): 1403–11. http://dx.doi.org/10.1515/pac-2016-1123.
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AbstractStreptococcus pneumoniae can cause many types of dangerous infectious diseases such as otitis media, pneumonia, meningitis and others that are more common in the very young and very old age. Available to date commercial vaccines based on capsular polysaccharides of S. pneumoniae of clinically important strains (first generation carbohydrate vaccines) and conjugated vaccines based on these polysaccharides (second generation carbohydrate vaccines) have certain limitations in protective efficiency. However, the efficiency of vaccines can be increased by the use of third generation vaccines based on synthetic oligosaccharide ligands representing in their structures the protective epitopes of capsular polysaccharides. The proper choice of an optimal oligosaccharide ligand is the most important step in the design of third generation carbohydrate vaccines. Herein we overview our works on the synthesis of three oligosaccharides corresponding to one, “one and a half” and two repeating units of S. pneumoniae type 14 capsular polysaccharide, immunogenic conjugates thereof and comparative immunological study of their conjugates with bovine serum albumin, which was used as a model protein carrier. The ability of obtained products to raise antibodies specific to capsular polysaccharide and homologous oligosaccharides, the induction of phagocytosis by immune antisera and active protection of immunized animals from S. pneumoniae type 14 infection were evaluated. On the basis of the results obtained tetrasaccharide comprising the repeating unit of S. pneumoniae type 14 capsular polysaccharide is an optimal carbohydrate ligand to be used as a part of the third generation carbohydrate pneumococcal vaccine.
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Gill, Christopher, Pejman Rohani, and Donald M. Thea. "The relationship between mucosal immunity, nasopharyngeal carriage, asymptomatic transmission and the resurgence of Bordetella pertussis." F1000Research 6 (August 25, 2017): 1568. http://dx.doi.org/10.12688/f1000research.11654.1.
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The incidence of whooping cough in the US has been rising slowly since the 1970s, but the pace of this has accelerated sharply since acellular pertussis vaccines replaced the earlier whole cell vaccines in the late 1990s. A similar trend occurred in many other countries, including the UK, Canada, Australia, Ireland, and Spain, following the switch to acellular vaccines. The key question is why. Two leading theories (short duration of protective immunologic persistence and evolutionary shifts in the pathogen to evade the vaccine) explain some but not all of these shifts, suggesting that other factors may also be important. In this synthesis, we argue that sterilizing mucosal immunity that blocks or abbreviates the duration of nasopharyngeal carriage of Bordetella pertussis and impedes person-to-person transmission (including between asymptomatically infected individuals) is a critical factor in this dynamic. Moreover, we argue that the ability to induce such mucosal immunity is fundamentally what distinguishes whole cell and acellular pertussis vaccines and may be pivotal to understanding much of the resurgence of this disease in many countries that adopted acellular vaccines. Additionally, we offer the hypothesis that observed herd effects generated by acellular vaccines may reflect a modification of disease presentation leading to reduced potential for transmission by those already infected, as opposed to inducing resistance to infection among those who have been exposed.
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Li, Fuying, Kejun Cheng, Joshua F. G. Antoline, Malliga R. Iyer, Gary R. Matyas, Oscar B. Torres, Rashmi Jalah, et al. "Synthesis and immunological effects of heroin vaccines." Org. Biomol. Chem. 12, no. 37 (2014): 7211–32. http://dx.doi.org/10.1039/c4ob01053a.
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Pozsgay, Vince. "Synthesis of Glycoconjugate Vaccines againstShigella dysenteriaeType 1." Journal of Organic Chemistry 63, no. 17 (August 1998): 5983–99. http://dx.doi.org/10.1021/jo980660a.
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Behera, Archanamayee, and Suvarn Kulkarni. "Chemical Synthesis of Rare, Deoxy-Amino Sugars Containing Bacterial Glycoconjugates as Potential Vaccine Candidates." Molecules 23, no. 8 (August 10, 2018): 1997. http://dx.doi.org/10.3390/molecules23081997.
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Bacteria often contain rare deoxy amino sugars which are absent in the host cells. This structural difference can be harnessed for the development of vaccines. Over the last fifteen years, remarkable progress has been made toward the development of novel and efficient protocols for obtaining the rare sugar building blocks and their stereoselective assembly to construct conjugation ready bacterial glycans. In this review, we discuss the total synthesis of a variety of rare sugar containing bacterial glycoconjugates which are potential vaccine candidates.
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Popov, Yu A., and N. I. Mikshis. "Genetic (DNA) Vaccines." Problems of Particularly Dangerous Infections, no. 3(105) (June 20, 2010): 20–24. http://dx.doi.org/10.21055/0370-1069-2010-3(105)-20-24.
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With the development of various branches of medicine and biology the classical ideas about means to prevent infectious diseases have changed. Nowadays in different countries of the world, investigations are carried out intensively in the sphere of genetic vaccines. Distinctive feature of DNA-vaccination is long lasted expression in eukaryotic cell cytoplasm of nucleic acids encoding synthesis of immunogenic proteins. Genetic vaccines induce both humoral and cellular responses accompanied by production of large pool of immunological memory cells. A number of questions regarding features of gene-engineered construction and transfer of DNA-vaccines into the cells of macroorganism, structure of DNA-vaccines and mechanisms of immune response generation are considered in the review. Attention is paid on the safety of gene vaccination and ways to improve its efficiency.
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Hanna, Cameron C., Anneliese S. Ashhurst, Diana Quan, Joshua W. C. Maxwell, Warwick J. Britton, and Richard J. Payne. "Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice." Proceedings of the National Academy of Sciences 118, no. 4 (January 19, 2021): e2013730118. http://dx.doi.org/10.1073/pnas.2013730118.
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The global incidence of tuberculosis remains unacceptably high, with new preventative strategies needed to reduce the burden of disease. We describe here a method for the generation of synthetic self-adjuvanted protein vaccines and demonstrate application in vaccination against Mycobacterium tuberculosis. Two vaccine constructs were designed, consisting of full-length ESAT6 protein fused to the TLR2-targeting adjuvants Pam2Cys-SK4 or Pam3Cys-SK4. These were produced by chemical synthesis using a peptide ligation strategy. The synthetic self-adjuvanting vaccines generated powerful local CD4+ T cell responses against ESAT6 and provided significant protection in the lungs from virulent M. tuberculosis aerosol challenge when administered to the pulmonary mucosa of mice. The flexible synthetic platform we describe, which allows incorporation of adjuvants to multiantigenic vaccines, represents a general approach that can be applied to rapidly assess vaccination strategies in preclinical models for a range of diseases, including against novel pandemic pathogens such as SARS-CoV-2.
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Zarei, Adi Essam, Hussein A. Almehdar, and Elrashdy M. Redwan. "Hib Vaccines: Past, Present, and Future Perspectives." Journal of Immunology Research 2016 (2016): 1–18. http://dx.doi.org/10.1155/2016/7203587.
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Haemophilus influenzaetype b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5–10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method) and cross-linked lattice matrix (dual amination method). Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy.
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Bazhan, Sergei I., Denis V. Antonets, Larisa I. Karpenko, Svetlana F. Oreshkova, Olga N. Kaplina, Ekaterina V. Starostina, Sergei G. Dudko, Sofia A. Fedotova, and Alexander A. Ilyichev. "In silico Designed Ebola Virus T-Cell Multi-Epitope DNA Vaccine Constructions Are Immunogenic in Mice." Vaccines 7, no. 2 (March 29, 2019): 34. http://dx.doi.org/10.3390/vaccines7020034.
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Background: The lack of effective vaccines against Ebola virus initiates a search for new approaches to overcoming this problem. The aim of the study was to design artificial polyepitope T-cell immunogens––candidate DNA vaccines against Ebola virus and to evaluate their capacity to induce a specific immune response in a laboratory animal model. Method: Design of two artificial polyepitope T-cell immunogens, one of which (EV.CTL) includes cytotoxic and the other (EV.Th)––T-helper epitopes of Ebola virus proteins was carried out using original TEpredict/PolyCTLDesigner software. Synthesized genes were cloned in pcDNA3.1 plasmid vector. Target gene expression was estimated by synthesis of specific mRNAs and proteins in cells transfected with recombinant plasmids. Immunogenicity of obtained DNA vaccine constructs was evaluated according to their capacity to induce T-cell response in BALB/c mice using IFNγ ELISpot and ICS. Results: We show that recombinant plasmids pEV.CTL and pEV.Th encoding artificial antigens provide synthesis of corresponding mRNAs and proteins in transfected cells, as well as induce specific responses both to CD4+ and CD8+ T-lymphocytes in immunized animals. Conclusions: The obtained recombinant plasmids can be regarded as promising DNA vaccine candidates in future studies of their capacity to induce cytotoxic and protective responses against Ebola virus.
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Samantaray, Utkalendu Suvendusekhar, and Rudra Prasad Khuntia. "mRNA vaccines against emerging infectious diseases; A challenging approach of novel vaccine discovery." International Journal of Medical, Pharmacy and Drug Research 6, no. 2 (2022): 52–57. http://dx.doi.org/10.22161/ijmpd.6.2.7.
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Basic human biology is dealt with by mRNA, which creates instructions for making proteins that may aid in the fight against infectious illnesses using our bodies' own mechanisms. mRNA therapies are neither tiny compounds nor huge biological such as recombinant proteins or monoclonal antibodies. These are a series of instructions that assist our cells' machinery in producing proteins that protect us against a certain virus. Our bodies would be unable to perform their activities if mRNA was not introduced. mRNA, or messenger ribonucleic acid, is an important component of the living world, especially in the process of protein synthesis. mRNA is a single-stranded molecule that transmits genetic instructions from a cell's nucleus DNA to the ribosomes, which are the cell's protein-making machinery. The synthesis of an RNA copy from the coded sequence of DNA leads in the production of a particular protein. This copy of mRNA moves from the nucleus of the cell to the cytoplasm, where ribosomes reside. Ribosomes are a sort of sophisticated machinery organelle that aids and begins protein synthesis in cells. Ribosomes ‘read' the mRNA sequence and follow the instructions, progressively adding on various needed amino acids to make the intended protein during the translation process. The protein is subsequently expressed by the cell, and it goes on to execute its role in the cell or in the body. The use of mRNA as a medication offers up a whole new universe of possibilities in terms of illness treatment and prevention. This review contributes to the growing body of knowledge in the field of mRNA therapeutic delivery and the identification of appropriate antigens for mRNA target locations. Two major mRNA vaccines for protection against SARS-CoV-2 have recently been developed and approved for use in the general population by international health authorities. They've been demonstrated to defend against the SARS-CoV-2 virus, which is still active and evolving. This will draw attention to a variety of mRNA vaccines now being evaluated for infectious diseases in clinical studies. mRNA vaccines offer a number of advantages, including speedy design, fabrication, manufacturing, and administration, and they hold a lot of potential for future use against a wide range of diseases.
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Köteles, István, and Sándor Hosztafi. "Vaccines against Drug Abuse: Morphine-Hapten Design and Synthesis." Proceedings 41, no. 1 (November 14, 2019): 48. http://dx.doi.org/10.3390/ecsoc-23-06473.
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Drugs of abuse are small molecules that typically do not induce an antibody response following the administration. To induce antibodies against these kind of molecules, structural changes have to be made to obtain so called “haptens”. The hapten must be coupled to immunogenic proteins, called “carriers”. These connected derivatives are typically drug-linker adducts, in which the linker has a terminal functional group (i.e., carboxylic acid or aliphatic amine) that forms a covalent bond with the carrier. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant. Six nor-normorphine compounds were reacted with ethyl acrylate and ethyl bromoacetate. After the synthesis of the specific esters we hydrolyzed them to receive the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives. The next step was the coupling phase with glycine ethyl ester, but the reactions didn’t work or the work-up process was not accomplishable. As an alternative route the normorphine-compounds were reacted with N-chloroacetyl glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine sidechain. All of the glycine ester and the glycine carboxylic acid derivatives are under biological tests.
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Frolov, S. V., L. O. Scherbakova, N. V. Moroz, V. N. Irza, and V. Yu Kulakov. "Comparative testing of vaccines based on viruses of genetic lineages G1 and Y280 for their potency against low pathogenic avian influenza H9N2." Veterinary Science Today, no. 3 (August 17, 2021): 224–29. http://dx.doi.org/10.29326/2304-196x-2021-3-38-224-229.
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Due to the genetic diversity of low pathogenic avian influenza (LPAI) viruses of subtype H9N2, it deemed appropriate to study the potency of the vaccines based on the antigens of strains А/chicken/Amursky/03/12 and A/chicken/Chelyabinsk/314-1/20 that represent currently circulating in the Russian Federation genetic lineages Y280 and G1, respectively. While low pathogenicity of the agent does not allow demonstrating the vaccine protective properties by the direct methods generally used for potency assessment (e.g. morbidity and mortality), the indirect methods were used: determination of antigenic relatedness of the strains, level of the postvaccinal homologous and heterologous humoral immunity, analysis of the virus genome synthesis inhibition (reduction) in vaccinated birds following their challenge. The strains used in the vaccines were determined to have some antigenic differences, which were demonstrated in the hemagglutination inhibition (HI) assay during control of the postvaccinal immunity in birds. Both vaccines generally induced strong humoral immunity in vaccinated birds (9–10 log2 determined using HI assay) with some difference in the levels of the immune response following the use of homologous or heterologous antigens. It was also reliably determined that homologous immunity facilitated more expressed inhibition of the virus reproduction after the challenge. The level of inhibition (reduction) of the virulent LPAI virus genome synthesis in vaccinated birds following their challenge with H9N2 virus of genetic lineage G1 was higher in birds following homologous vaccination, while the time periods of the genome detection in the biomaterial samples were the same. It was demonstrated that due to antigenic and immunogenic differences between LPAI H9N2 strains, use of both antigenic components in the inactivated vaccines is appropriate.
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Ghorbani, Amir, Michael C. Abundo, Hana Ji, Kara J. M. Taylor, John M. Ngunjiri, and Chang-Won Lee. "Viral Subpopulation Screening Guides in Designing a High Interferon-Inducing Live Attenuated Influenza Vaccine by Targeting Rare Mutations in NS1 and PB2 Proteins." Journal of Virology 95, no. 2 (October 28, 2020): e01722-20. http://dx.doi.org/10.1128/jvi.01722-20.
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ABSTRACTInfluenza A viruses continue to circulate among wild birds and poultry worldwide, posing constant pandemic threats to humans. Effective control of emerging influenza viruses requires new broadly protective vaccines. Live attenuated influenza vaccines with truncations in nonstructural protein 1 (NS1) have shown broad protective efficacies in birds and mammals, which correlate with the ability to induce elevated interferon responses in the vaccinated hosts. Given the extreme diversity of influenza virus populations, we asked if we could improve an NS1-truncated live attenuated influenza vaccine developed for poultry (PC4) by selecting viral subpopulations with enhanced interferon-inducing capacities. Here, we deconstructed a de novo population of PC4 through plaque isolation, created a large library of clones, and assessed their interferon-inducing phenotypes. While most of the clones displayed the parental interferon-inducing phenotype in cell culture, few clones showed enhanced interferon-inducing phenotypes in cell culture and chickens. The enhanced interferon-inducing phenotypes were linked to either a deletion in NS1 (NS1Δ76-86) or a substitution in polymerase basic 2 protein (PB2-D309N). The NS1Δ76-86 deletion disrupted the putative eukaryotic translation initiation factor 4GI-binding domain and promoted the synthesis of biologically active interferons. The PB2-D309N substitution enhanced the early transcription of interferon mRNA, revealing a novel role for the 309D residue in suppression of interferon responses. We combined these mutations to engineer a novel vaccine candidate that induced additive amounts of interferons and stimulated protective immunity in chickens. Therefore, viral subpopulation screening approaches can guide the design of live vaccines with strong immunostimulatory properties.IMPORTANCE Effectiveness of NS1-truncated live attenuated influenza vaccines relies heavily on their ability to induce elevated interferon responses in vaccinated hosts. Influenza viruses contain diverse particle subpopulations with distinct phenotypes. We show that live influenza vaccines can contain underappreciated subpopulations with enhanced interferon-inducing phenotypes. The genomic traits of such virus subpopulations can be used to further improve the efficacy of the current live vaccines.
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Wu, Xiangyang, and David R. Bundle. "Synthesis of Glycoconjugate Vaccines forCandidaalbicansUsing Novel Linker Methodology." Journal of Organic Chemistry 70, no. 18 (September 2005): 7381–88. http://dx.doi.org/10.1021/jo051065t.
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Dziadek, Sebastian, Carmen G. Espínola, and Horst Kunz. "Synthetic Glycopeptides for the Development of Antitumour Vaccines." Australian Journal of Chemistry 56, no. 6 (2003): 519. http://dx.doi.org/10.1071/ch02241.
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Glycoproteins of tumour cells often are aberrantly glycosylated. In its tumour-associated form, the epithelial mucin MUC1 carries short saccharide structures such as TN, T, sialyl-TN, and sialyl-T antigens. Due to the incomplete saccharide components, peptide epitopes of the backbone become accessible to the immune system. For the construction of synthetic antitumour vaccines, glycopeptides have been synthesized which contain tumour-associated saccharide antigens and peptide sequences from the tandem repeat portion of MUC1. In the synthesis of these glycopeptides, preformed glycosyl–amino acid building blocks are applied in solution- or solid-phase strategies. Examples are given for the use of N-Fmoc-protected TN, T, sialyl-TN, and sialyl-T antigen–serine and –threonine conjugates in syntheses of glycopeptides from the tandem repeat region from MUC1 and the N-terminal portion of leukosialin (CD43). In solid-phase syntheses allylic linkers (cleavable under neutral conditions), acid-sensitive linkers, and the novel 2-phenyl-2-trimethylsilyl-ethyl ester linker (detachable with fluoride under neutral conditions) have successfully been applied. The synthetic tumour-associated glycopeptide antigens, identical to nature, often exhibit low immunogenicity. Therefore, their conjugation to carrier proteins is demanded. To this aim, glycopeptide antigens have been equipped with biotin labels or conjugated with T-cell peptide epitopes. Some of these synthetic glycopeptide antigens induce proliferation of T-cells and a cytotoxic T-cell response.
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Zaitsev, A. E., E. A. Kurbatova, N. B. Egorova, E. V. Sukhova, and N. E. Nifantiev. "Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines." Journal of microbiology epidemiology immunobiology, no. 1 (March 6, 2020): 72–82. http://dx.doi.org/10.36233/0372-9311-2020-1-72-82.
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The introduction of pneumococcal vaccines into national immunization programmes around the world has reduced the incidence of pneumococcal vaccine serotypes, but had no influence on the incidence of Streptococcus pneumoniae serotype 3 included in their composition. The results of evaluation of epidemiological efficacy and immunogenicity of capsular polysaccharide of S. pneumoniae serotype 3 capsular polysaccharide (CP) in conjugated and polysaccharide pneumococcal vaccines are contradictory. Some studies have shown the effectiveness of vaccination, other studies indicate insufficient immunogenicity and prophylactic efficacy of S. pneumoniae serotype 3 CP. The authors’ analysis of the results of clinical studies showed that the prophylactic efficacy of S. pneumoniae serotype 3 CP depends on the type of vaccine, nosological form of the disease, age, immunization schedule. According to the literature data, the most informative parameter of the protective activity of S. pneumoniae CP in pneumococcal vaccines, including serotype 3, is opsonophagocytosis. The experimental data of the low immunogenicity of serotype 3 CP, presumably associated with an unusual way of synthesis of its CP, are considered. To increase the im muno genicity of S. pneumoniae serotype 3 CP, the use of synthetic oligosaccharides of a strictly defined chemical structure corresponding to the protective fragments of serotype 3 CP and conjugated with a carrier protein for induction of T-dependent immune response and immunological memory is promising.
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Zaitsev, A. E., E. A. Kurbatova, N. B. Egorova, E. V. Sukhova, and N. E. Nifantiev. "Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines." Journal of microbiology, epidemiology and immunobiology 97, no. 1 (April 2, 2020): 72–82. http://dx.doi.org/10.36233/0372-9311-2020-97-1-72-82.
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The introduction of pneumococcal vaccines into national immunization programmes around the world has reduced the incidence of pneumococcal vaccine serotypes, but had no influence on the incidence of Streptococcus pneumoniae serotype 3 included in their composition. The results of evaluation of epidemiological efficacy and immunogenicity of capsular polysaccharide of S. pneumoniae serotype 3 capsular polysaccharide (CP) in conjugated and polysaccharide pneumococcal vaccines are contradictory. Some studies have shown the effectiveness of vaccination, other studies indicate insufficient immunogenicity and prophylactic efficacy of S. pneumoniae serotype 3 CP. The authors’ analysis of the results of clinical studies showed that the prophylactic efficacy of S. pneumoniae serotype 3 CP depends on the type of vaccine, nosological form of the disease, age, immunization schedule. According to the literature data, the most informative parameter of the protective activity of S. pneumoniae CP in pneumococcal vaccines, including serotype 3, is opsonophagocytosis. The experimental data of the low immunogenicity of serotype 3 CP, presumably associated with an unusual way of synthesis of its CP, are considered. To increase the im muno genicity of S. pneumoniae serotype 3 CP, the use of synthetic oligosaccharides of a strictly defined chemical structure corresponding to the protective fragments of serotype 3 CP and conjugated with a carrier protein for induction of T-dependent immune response and immunological memory is promising.
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Fishman, Jordan, Leonard Moise, Pierre LeBlanc, Timothy Brauns, Eric Berg, Daniel Richer, Christine Boyle, et al. "VaxCelerate: the use of MTBhsp70-avidin as an adjuvant to rapidly generate self-assembling vaccines with biotinylated, antigen-specific peptides targeting emerging pathogens. (VAC6P.941)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 140.2. http://dx.doi.org/10.4049/jimmunol.192.supp.140.2.
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Abstract Development of effective vaccines against emerging infectious diseases can take years to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. The VaxCelerate Project’s goal is to create a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 days. A self-assembling vaccine, consisting of a fusion protein M. tuberculosis MTBhsp70 and avidin (MAV), is at the core of the approach. Mixing the MAV with biotinylated pathogen specific immunogenic peptides yields a self-assembled vaccine (SAV). To minimize the time required, we used a distributed R&D model involving experts in protein engineering, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing. This approach was first tested using ovalbumin in C57Bl/6 mice, Flu (H1N1) specific peptides, and ultimately a Lassa fever virus (LFV) specific vaccine in transgenic HLA DR3 mice. Using a GLP validated assay we demonstrated that the MAV assembled LFV induced significantly increased class II peptide specific interferon-CD4+ T cell responses in transgenic mice compared to peptide or MAV alone controls. The use of an identical design for each vaccine may facilitate accelerated regulatory review and by developing safety assessment tools that are more relevant to human vaccine responses than current preclinical models.