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Bondarev, V. P., V. A. Shevtsov, I. N. Indikova, E. E. Evreinova, and D. V. Gorenkov. "Rotavirus Epidemiology and Vaccination Tactics." BIOpreparations. Prevention, Diagnosis, Treatment 19, no. 2 (June 16, 2019): 81–87. http://dx.doi.org/10.30895/2221-996x-2019-19-2-81-87.
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Rotavirus infection is a widespread cause of severe gastroenteritis in children in low-income countries. Specific prophylaxis in young children has become the most important means of combating severe rotavirus gastroenteritis. The review presents current data on the molecular biology and genetic diversity of rotaviruses, interaction of viral proteins with host cell receptors, molecular aspects of infectivity and pathogenesis of rotavirus infection, and the development of immunity. It addresses a new approach to the epidemiology of rotavirus infection which regards it as a manageable infection, it illustrates the specificity of the epidemic process based on data gained from extensive experience in vaccination, and summarises relevant information on the introduction of rotavirus vaccines into the international healthcare practice. The paper summarises risks associated with the use of vaccines based on the analysis of WHO statistics, scientific publications on the epidemiology of rotavirus infection, and the results of vaccination. It analyses approaches of the competent authorities of some countries to the tactics of vaccination against rotavirus infection and the WHO stance on the use of existing vaccines for the prevention of rotavirus infection. A conclusion was made that it is necessary to further improve the tactics of vaccine prevention of rotavirus infection in Russia, to study the incidence of idiopathic intussusception, and to conduct further studies aimed at characterisation of existing and newly emerging genotypes of rotavirus.
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PIKUŁA, ANNA, and KRZYSZTOF ŚMIETANKA. "Selected aspects of infectious bursal disease – the current state of knowledge." Medycyna Weterynaryjna 74, no. 10 (2023): 6138–2023. http://dx.doi.org/10.21521/mw.6138.
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Infectious bursal disease (IBD) is a highly infectious and contagious immunosuppressive viral disease of chickens with a worldwide economic significance to the poultry industry. Over fifty years have passed since the first confirmed occurrence of the disease, and the virus has spread all over world and evolved into multiple genetic, antigenic and pathotypic variants, becoming a serious threat to the poultry industry. The primary tool in IBD eradication is the maintenance of strict biosecurity in poultry farms and implementation of vaccination programmes which should take into account the current epidemiological knowledge about the IBDV strains circulating in the field. This review article presents the current state of knowledge about the infectious bursal disease virus (IBDV) with special regard to the molecular biology of the virus, immunological aspects, as well as current and future prevention strategies.
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Teale, Alan. "Biotechnology: a key element in the CGIAR's livestock research programme." Outlook on Agriculture 26, no. 4 (December 1997): 217–25. http://dx.doi.org/10.1177/003072709702600403.
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The unique potential of biotechnology to provide new solutions to old problems constraining the contribution of livestock to farming systems in the developing world is emphasized in this paper. An overview of biotechnological aspects of livestock research within the CGIAR, including a description of the research approaches being adopted at the International Livestock Research Institute, is provided. The products of the research are then identified, and their potential applications in disease diagnosis and vaccination, as well as in the fields of animal breeding and genetic improvement, are described.
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HELGESSON, GERT, and STEFAN ERIKSSON. "Four Themes in Recent Swedish Bioethics Debates." Cambridge Quarterly of Healthcare Ethics 20, no. 3 (May 20, 2011): 409–17. http://dx.doi.org/10.1017/s0963180111000090.
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A wide variety of bioethical themes have recently been debated and researched in Sweden, including genetic screening, HPV vaccination strategies, end-of-life care, injustices and priority setting in healthcare, dual-use research, and the never-ending story of scientific fraud. Also, there are some new events related to Swedish biobanking that might be of general interest. Here we will concentrate on four themes: end-of-life care, dual-use research, scientific fraud, and biobanking.
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Mehra, Narinder K., and Gurvinder Kaur. "MHC-based vaccination approaches: progress and perspectives." Expert Reviews in Molecular Medicine 5, no. 7 (February 24, 2003): 1–17. http://dx.doi.org/10.1017/s1462399403005957.
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The major histocompatibility complex (MHC) harbours genes whose primary function in regulating immune responsiveness to infection is to present foreign antigens to cytotoxic T lymphocytes (CTLs) and T helper cells. In the case of infection by human immunodeficiency virus (HIV), defining the optimal HIV epitopes that are recognised by CTLs is important for vaccine design, and this in turn will depend on the characteristics of the predominant infecting virus. Moreover, the particular MHC human leukocyte antigens (HLAs) expressed by a geographical population is important since these are likely to determine which HIV epitopes are immunodominant in the anti-HIV immune response. Consideration of these aspects has lead to the dawn of a new era of MHC-based vaccine design, in which the CTL epitopes are selected on the basis of the frequency of restricting MHC alleles. This article reviews data on the distribution patterns of molecular subtypes of HLA class I and class II extended haplotypes, discussing distribution among Asian Indians but with reference to global distributions. These data provide a genetic basis for the possible predisposition and fast progression of HIV infections in the Indian population. Since there is selective predominance of different HLA alleles and haplotypes in different populations, a dedicated screening effort is required at the global level to develop MHC-based vaccines against infectious diseases. It is hoped that this might lead to the development of multivalent, poly-epitope, subtype-specific HIV vaccines that are specific for the target geographical location.
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Tusup, Marina, Lars E. French, Mara De Matos, David Gatfield, Thomas Kundig, and Steve Pascolo. "Design of in vitro Transcribed mRNA Vectors for Research and Therapy." CHIMIA International Journal for Chemistry 73, no. 5 (May 29, 2019): 391–94. http://dx.doi.org/10.2533/chimia.2019.391.
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The use of in vitro transcribed messenger RNA (ivt mRNA) for vaccination, gene therapy and cell reprograming has become increasingly popular in research and medicine. This method can be used in vitro (transfected in cells) or administered naked or formulated (lipoplexes, polyplexes, and lipopolyplexes that deliver the RNA to specific organs, such as immune structures, the lung or liver) and is designed to be an immunostimulatory or immunosilent agent. This vector contains several functional regions (Cap, 5' untranslated region, open reading frame, 3' untranslated region and poly-A tail) that can all be optimised to generate a highly efficacious ivt mRNA. In this study, we review these aspects and report on the effect of the ivt mRNA purification method on the functionality of this synthetic transient genetic vector.
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Ambinder, Alexander J., Pareen J. Shenoy, Neha Malik, Alison Maggioncalda, Loretta J. Nastoupil, and Christopher R. Flowers. "Exploring Risk Factors for Follicular Lymphoma." Advances in Hematology 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/626035.
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Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with varied incidence across racial groups and geographic regions. Improvements in the classification of non-Hodgkin lymphoma subtypes provide an opportunity to explore associations between environmental exposures and FL incidence. Our paper found that aspects of Western lifestyle including sedentary lifestyle, obesity, and diets high in meat and milk are associated with an increased risk of FL. Diets rich in fruits and vegetables, polyunsaturated fatty acids, vitamin D, and certain antioxidants are inversely associated with FL risk. A medical history of Sjogren's syndrome, influenza vaccination, and heart disease may be associated with FL incidence. Associations between FL and exposure to pesticides, industrial solvents, hair dyes, and alcohol/tobacco were inconsistent. Genetic risk factors include variants at the 6p21.32 region of the MHC II locus, polymorphisms of the DNA repair geneXRCC3, and UV exposure in individuals with certain polymorphisms of the vitamin D receptor. Increasing our understanding of risk factors for FL must involve integrating epidemiological studies of genetics and exposures to allow for the examination of risk factors and interactions between genes and environment.
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Eckmann, Lars, and Frances D. Gillin. "Microbes and Microbial Toxins: Paradigms for Microbial- Mucosal Interactions I. Pathophysiological aspects of enteric infections with the lumen-dwelling protozoan pathogenGiardia lamblia." American Journal of Physiology-Gastrointestinal and Liver Physiology 280, no. 1 (January 1, 2001): G1—G6. http://dx.doi.org/10.1152/ajpgi.2001.280.1.g1.
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Giardia lamblia is one of the most important causes of waterborne diarrheal disease worldwide, and giardiasis is the most common protozoan infection of the human small intestine. Symptomatic infection is characterized by diarrhea, abdominal pain, and malabsorption, leading to malnutrition and weight loss, particularly in children. The pathogen resides strictly in the lumen of the small intestine, and infection is typically not accompanied by significant mucosal inflammation. Clinical and experimental studies indicate that B cell-dependent host defenses, particularly IgA, are important for controlling and clearing Giardia infection, although B cell-independent mechanisms also contribute to this outcome. In contrast to antigiardial host defenses, much less is known about the pathophysiological mechanisms underlying the clinical symptoms of giardiasis, partly because of the current lack of suitable model systems. In addition to being an important human enteric pathogen, Giardia is an interesting model organism for gaining basic insights into genetic innovations that led to evolution of eukaryotic cells, since it belongs to the earliest diverging eukaryotic lineage known. The completion of the giardial genome project will increase understanding of the basic biology of the protozoan and will help us to better understand host pathogen-interactions as a basis for developing new vaccination and therapeutic strategies.
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Eckert, Johannes, and Peter Deplazes. "Biological, Epidemiological, and Clinical Aspects of Echinococcosis, a Zoonosis of Increasing Concern." Clinical Microbiology Reviews 17, no. 1 (January 2004): 107–35. http://dx.doi.org/10.1128/cmr.17.1.107-135.2004.
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SUMMARY Echinococcosis in humans is a zoonotic infection caused by larval stages (metacestodes) of cestode species of the genus Echinococcus. Cystic echinococcosis (CE) is caused by Echinococcus granulosus, alveolar echinococcosis (AE) is caused by E. multilocularis, and polycystic forms are caused by either E. vogeli or E. oligarthrus. In untreated cases, AE has a high mortality rate. Although control is essentially feasible, CE remains a considerable health problem in many regions of the northern and southern hemispheres. AE is restricted to the northern hemisphere regions of North America and Eurasia. Recent studies have shown that E. multilocularis, the causative agent of AE, is more widely distributed than previously thought. There are also some hints of an increasing significance of polycystic forms of the disease, which are restricted to Central and South America. Various aspects of human echinococcosis are discussed in this review, including data on the infectivity of genetic variants of E. granulosus to humans, the increasing invasion of cities in Europe and Japan by red foxes, the main definitive hosts of E. multilocularis, and the first demonstration of urban cycles of the parasite. Examples of emergence or reemergence of CE are presented, and the question of potential spreading of E. multilocularis is critically assessed. Furthermore, information is presented on new and improved tools for diagnosing the infection in final hosts (dogs, foxes, and cats) by coproantigen or DNA detection and the application of molecular techniques to epidemiological studies. In the clinical field, the available methods for diagnosing human CE and AE are described and the treatment options are summarized. The development of new chemotherapeutic options for all forms of human echinococcosis remains an urgent requirement. A new option for the control of E. granulosus in the intermediate host population (mainly sheep and cattle) is vaccination. Attempts are made to reduce the prevalence of E. multilocualaris in fox populations by regular baiting with an anthelmintic (praziquantel). Recent data have shown that this control option may be used in restricted areas, for example in cities, with the aim of reducing the infection risk for humans.
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Sang, Helen. "DISEASE RESISTANCE AND OTHER APPLICATIONS OF TRANSGENESIS IN THE CHICKEN." Reproduction, Fertility and Development 25, no. 1 (2013): 320. http://dx.doi.org/10.1071/rdv25n1ab345.
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Genetic modification of the chicken in terms of gene addition is now robust and efficient. Transgenes can be introduced by injection of lentiviral vectors into chick embryos or by transfection of transposon vectors into embryos or primordial germ cells in vitro. Lentiviral vectors are limited in the size of transgene they can incorporate but we have generated several different transgenic lines using HIV-derived vectors and have observed high levels of transgene expression and tissue-specific expression using regulatory sequences from several genes. M. McGrew (The Roslin Institute) has established primordial germ cell lines and effective methods for transfection with piggyBac and Tol2 transposon vectors. The primordial cells are injected into chick embryos where they populate the developing gonads and contribute to the germline in mature birds. The availability of primordial germ cell lines will also form the basis of using artificial site-specific nucleases for gene knockout and potentially gene targeting in the chicken. These technologies facilitate the application of transgenesis in the chicken for basic research and for potential applications in poultry breeding. The chick embryo is an invaluable model for studying vertebrate development as the embryos can be accessed in ovo or in culture at the earlier stages of development. Embryos can be transfected with transgenes by electroporation and manipulated to study many aspects of development. We are developing transgenic chickens in which fluorescent protein reporters are expressed either ubiquitously or in targeted cell types. These form the basis of novel tools for increasing the value of the chick embryo in studying development. We provide fertile eggs from these lines to other research groups and are investigating the development of macrophages using a macrophage-targeted reporter. The potential for the use of genetic modification to be used in poultry breeding can now be explored. Commercial poultry production is challenged by several major pathogens including avian influenza. Flocks can be protected by good biosecurity measures and/or vaccination but vaccination is not always effective. It may be possible to add novel genes to the chicken genome targeting avian influenza virus replication. We are developing this approach (with L. Tiley, Cambridge University) and have generated transgenic chickens that do not transmit avian influenza when directly infected with H5N1 virus.
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Omersel, Jasna, and Nataša Karas Kuželički. "Vaccinomics and Adversomics in the Era of Precision Medicine: A Review Based on HBV, MMR, HPV, and COVID-19 Vaccines." Journal of Clinical Medicine 9, no. 11 (November 5, 2020): 3561. http://dx.doi.org/10.3390/jcm9113561.
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Precision medicine approaches based on pharmacogenomics are now being successfully implemented to enable physicians to predict more efficient treatments and prevention strategies for a given disease based on the genetic background of the patient. This approach has already been proposed for vaccines, but research is lagging behind the needs of society, and precision medicine is far from being implemented here. While vaccinomics concerns the effectiveness of vaccines, adversomics concerns their side effects. This area has great potential to address public concerns about vaccine safety and to promote increased public confidence, higher vaccination rates, and fewer serious adverse events in genetically predisposed individuals. The aim here is to explore the contemporary scientific literature related to the vaccinomic and adversomic aspects of the three most-controversial vaccines: those against hepatitis B, against measles, mumps, and rubella, and against human Papilloma virus. We provide detailed information on the genes that encode human leukocyte antigen, cytokines and their receptors, and transcription factors and regulators associated with the efficacy and safety of the Hepatitis B and Measles, Mumps and Rubella virus vaccines. We also investigate the future prospects of vaccinomics and adversomics of a COVID-19 vaccine, which might represent the fastest development of a vaccine ever.
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Pershing, Nicole L., Aurélie Kapusta, Shannon Nielsen, Hillary Crandall, E. Kent Korgenski, Carrie L. Byington, Krow Ampofo, and Anne J. Blaschke. "#64: An odyssey Beyond the Capsule: Genetic Determinants of Pediatric Invasive Streptococcus pneumoniae Empyema." Journal of the Pediatric Infectious Diseases Society 10, Supplement_1 (March 1, 2021): S7. http://dx.doi.org/10.1093/jpids/piaa170.021.
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Abstract Background Streptococcus pneumoniae is among the most common causes of invasive bacterial infections in children, including pneumonia, bacteremia, and meningitis. Over 90 different serotypes (ST) of pneumococcus exist, with enrichment of some ST within specific invasive phenotypes. Other than capsular genes, molecular determinants of particular invasive phenotypes remain largely unknown. Although vaccination targeting especially invasive ST capsular antigens has successfully decreased the incidence of invasive pneumococcal disease (IPD), new ST have emerged, suggesting methods to target other aspects of pneumococcal invasiveness are needed. Methods Pneumococcal isolates from IPD were collected from children presenting to Primary Children’s Hospital from 1996–2018. All viable isolates underwent next-generation sequencing (Illumina), quality control filtering for contamination and low coverage, de novo genome assembly with SPADES, and annotation with PROKKA. Clinical phenotypes were manually validated with physician chart review. Isolates were serotyped via Quelling and in silico using SeroBA. ROARY was used for pan-genome assembly, and SCOARY for microbial genome-wide association studies. RAxML was used for phylogenetic analysis. Results A total of 354 viable pneumococcal isolates were available for genomic analysis including a spectrum of invasive phenotypes: pneumonia (n = 138, of which 54 were complicated by empyema), CNS infection (n = 50), SSTI/bone infections (n = 42), and isolated bacteremia (n = 68). Thirteen samples were censored for poor coverage or genetic contamination. Invasive isolates spanned 37 capsular ST. The pneumococcal pan-genome comprised 6462 genes, of which only 23% were shared by at least 99% of samples. Phylogenetic relatedness resulted in clustering of some ST (e.g., ST1, ST3), whereas others (eg ST19A) were more broadly distributed. Empyema and meningitis phenotypes were distributed across the phylogenetic tree, but enriched in distinct clusters that crossed ST clusters. Genes involved in empyemagenic pneumococcal capsule production, and those implicated in sensing of preferred sugars or non-preferred sugar metabolism were statistically correlated with the empyema phenotype. Conclusion There is marked genetic diversity among invasive pneumococcal isolates, potentially contributing to the variability of disease phenotypes observed. Clustering of invasive phenotypes across ST suggests a genetic signature for invasive phenotypes other than capsule genes alone, further supported by enrichment of specific genes associated with alternative sugar metabolism in empyema isolates. Critical determinants of invasive phenotypes will inform future efforts at disease prevention and treatment.
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Usha, A. Lakshmi, M. Kusama Kumari, E. Radha Rani, and M. Ramadevi. "A Novel Technique for Intradermal Delivery of Drugs – Coated Polymeric Needles." Asian Journal of Research in Pharmaceutical Sciences 11, no. 2 (May 10, 2021): 133–39. http://dx.doi.org/10.52711/2231-5659.2021-11-2-7.
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The barrier properties of the topmost layer of the skin, stratum corneum have significant limitations for successful systemic delivery of a wide range of therapeutic molecules, especially macromolecules and genetic material. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing through the stratum corneum and directly translocating protein drugs into the systematic circulation. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform technique has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therap. As an alternative to hypodermic needles, coated polymer microneedles (MNs) are able to deliver drugs to subcutaneous tissues after being inserted into the skin. The dip-coating process is a versatile, rapid fabricating method that can form coated MNs in a short time. However, it is still a challenge to fabricate coated MNs with homogeneous and precise drug doses in the dip-coating process. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. The clinical potential and future translation of MNs are also discussed.
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Luz, Jean Carlos dos Santos da, Fernanda Antunes, Maria Alejandra Clavijo-Salomon, Emanuela Signori, Nayara Gusmão Tessarollo, and Bryan E. Strauss. "Clinical Applications and Immunological Aspects of Electroporation-Based Therapies." Vaccines 9, no. 7 (July 2, 2021): 727. http://dx.doi.org/10.3390/vaccines9070727.
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Reversible electropermeabilization (RE) is an ultrastructural phenomenon that transiently increases the permeability of the cell membrane upon application of electrical pulses. The technique was described in 1972 by Neumann and Rosenheck and is currently used in a variety of applications, from medicine to food processing. In oncology, RE is applied for the intracellular transport of chemotherapeutic drugs as well as the delivery of genetic material in gene therapies and vaccinations. This review summarizes the physical changes of the membrane, the particularities of bleomycin, and the immunological aspects involved in electrochemotherapy and gene electrotransfer, two important EP-based cancer therapies in human and veterinary oncology.
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Bazargan, Mohsen, Cheryl Wisseh, Edward Adinkrah, Hoorolnesa Ameli, Delia Santana, Sharon Cobb, and Shervin Assari. "Influenza Vaccination among Underserved African-American Older Adults." BioMed Research International 2020 (November 5, 2020): 1–9. http://dx.doi.org/10.1155/2020/2160894.
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Background. Racial disparities in influenza vaccination among underserved minority older adults are a public health problem. Understanding the factors that impact influenza vaccination behaviors among underserved older African-Americans could lead to more effective communication and delivery strategies. Aims. We aimed to investigate rate and factors associated with seasonal influenza vaccination among underserved African-American older adults. We were particularly interested in the roles of demographic factors, socioeconomic status, and continuity and patient satisfaction with medical care, as well as physical and mental health status. Methods. This community-based cross-sectional study recruited 620 African-American older adults residing in South Los Angeles, one of the most under-resources areas within Los Angeles County, with a population of over one million. Bivariate and multiple regression analyses were performed to document independent correlates of influenza vaccination. Results. One out of three underserved African-American older adults aged 65 years and older residing in South Los Angeles had never been vaccinated against the influenza. Only 49% of participants reported being vaccinated within the 12 months prior to the interview. One out of five participants admitted that their health care provider recommended influenza vaccination. However, only 45% followed their provider’s recommendations. Multivariate logistic regression shows that old-old (≥75 years), participants who lived alone, those with a lower level of continuity of care and satisfaction with the accessibility, availability, and quality of care, and participants with a higher number of depression symptoms were less likely to be vaccinated. As expected, participants who indicated that their physician had advised them to obtain a flu vaccination were more likely to be vaccinated. Our data shows that only gender was associated with self-report of being advised to have a flu shot. Discussion. One of the most striking aspects of this study is that no association between influenza vaccination and being diagnosed with chronic obstructive pulmonary disease or other major chronic condition was detected. Our study confirmed that both continuity of care and satisfaction with access, availability, and quality of medical care are strongly associated with current influenza vaccinations. We documented that participants with a higher number of depression symptoms were less likely to be vaccinated. Conclusion. These findings highlight the role that culturally acceptable and accessible usual source of care van play as a gatekeeper to facilitate and implement flu vaccination among underserved minority older adults. Consistent disparities in influenza vaccine uptake among underserved African-American older adults, coupled with a disproportionate burden of chronic diseases, places them at high risk for undesired outcomes associated with influenza. As depression is more chronic/disabling and is less likely to be treated in African-Americans, there is a need to screen and treat depression as a strategy to enhance preventive care management such as vaccination of underserved African-American older adults. Quantification of associations between lower vaccine uptake and both depression symptoms as well as living alone should enable health professionals target underserved African-American older adults who are isolated and suffer from depression to reduce vaccine-related inequalities.
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CAIRNS, ANDREW J. G. "Epidemics in Heterogeneous Populations: Aspects of Optimal Vaccination Policies." Mathematical Medicine and Biology 6, no. 3 (1989): 137–59. http://dx.doi.org/10.1093/imammb/6.3.137.
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Trucchi, Cecilia, Claudio Costantino, Vincenzo Restivo, Chiara Bertoncello, Francesca Fortunato, Silvio Tafuri, Daniela Amicizia, et al. "Immunization Campaigns and Strategies against Human Papillomavirus in Italy: The Results of a Survey to Regional and Local Health Units Representatives." BioMed Research International 2019 (July 4, 2019): 1–8. http://dx.doi.org/10.1155/2019/6764154.
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Objective. The study aimed to assess the impact of HPV immunization campaigns organizational aspects, the characteristics of immunization program (vaccination targets and type of offer), and communicative strategies adopted by four Italian administrative regions on vaccination coverage observed. Methods. From November 2017 to March 2018, regional and Local Health Units (LHUs) representatives were invited to complete an online survey including 54 questions evaluating vaccination invite systems, access systems to vaccination centres, reminder and recall systems, and adverse events surveillance. An overall descriptive analysis was conducted. Since observed vaccine coverage (VC) obtained in females (2002-2004 birth cohorts) was lower than objectives fixed by the Italian Ministry of Health, variables were assessed using the national VC mean obtained in the 2003 girls birth cohort as outcome. Results. Twenty-six LHUs belonging to 4 Northern and Southern Italian regions participated in the study. Organizational aspects significantly related to VC lower than the national mean were access to vaccine centres without appointment and parents’ reservation as appointment planning system. Recall systems for both the first and the second dose, including the appointment in the invitation letter, the availability of regional immunization registry, and education of healthcare workers on universal HPV immunization strategies, instead, were related to higher VC. As regards preadolescent immunization strategies, both VC obtained in girls and boys were far from the Ministerial goals. Only 20% of LHUs introduced multicohort female strategies while all LHUs adopted copayment targeting both men and women. Immunizations strategies targeting subjects at risk were implemented only in half of participating LHUs. Conclusions. VC observed in participating LHUs are largely lower than the national objectives in all anti-HPV vaccine targets. Both organizational and educational strategies have to be implemented to improve the VC goals.
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Brass, Anette, Lars Frelin, David R. Milich, Matti Sällberg, and Gustaf Ahlén. "Functional Aspects of Intrahepatic Hepatitis B Virus-specific T Cells Induced by Therapeutic DNA Vaccination." Molecular Therapy 23, no. 3 (March 2015): 578–90. http://dx.doi.org/10.1038/mt.2014.233.
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Baral, Toya Nath. "Immunobiology of African Trypanosomes: Need of Alternative Interventions." Journal of Biomedicine and Biotechnology 2010 (2010): 1–24. http://dx.doi.org/10.1155/2010/389153.
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Trypanosomiasis is one of the major parasitic diseases for which control is still far from reality. The vaccination approaches by using dominant surface proteins have not been successful, mainly due to antigenic variation of the parasite surface coat. On the other hand, the chemotherapeutic drugs in current use for the treatment of this disease are toxic and problems of resistance are increasing (see Kennedy (2004) and Legros et al. (2002)). Therefore, alternative approaches in both treatment and vaccination against trypanosomiasis are needed at this time. To be able to design and develop such alternatives, the biology of this parasite and the host response against the pathogen need to be studied. These two aspects of this disease with few examples of alternative approaches are discussed here.
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Furst, D., L. Lenz, M. Horton, D. Flake, E. Sasso, and M. E. Weinblatt. "AB1239 THE EFFECT OF INFLUENZA VACCINATION ON THE MULTI-BIOMARKER DISEASE ACTIVITY SCORE AND ITS COMPONENT BIOMARKERS IN HEALTHY SUBJECTS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1910–11. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1188.
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Background:The multi-biomarker disease activity (MBDA) blood test measures 12 protein biomarkers (IL-6, CRP, SAA, EGF, VEGF, VCAM, MMP-1, MMP-3, leptin, resistin, TNF-RI and YKL40). It uses a validated algorithm to provide a score on a scale of 1-100 for assessing disease activity in patients with rheumatoid arthritis (RA). The MBDA score reflects several molecular aspects of inflammation, including cytokines, acute phase reactants, growth factors, molecular adhesion, metalloproteinases and hormones. Insights gained by understanding how vaccination affects these biomarkers in healthy subjects - in whom the level of inflammation prior to vaccination should be low and stable - may aid the understanding of how vaccination affects patients with RA.Objectives:The goal of this study was to understand how immunization of healthy subjects with the influenza vaccine affects the assessment of inflammation with the MBDA score and its 12 biomarkers.Methods:A 4-strain influenza virus vaccine (Fluarix Quadrivalent, GlaxoSmithKline) was administered intramuscularly to 22 healthy volunteer subjects on October 24, 2018. Serum samples were obtained immediately prior to vaccination (baseline) and 1, 2 and 3 weeks after vaccination. No restrictions were placed on subject activity. Samples were stored at -80oC until measurement of the 12 MBDA biomarkers for determination of the adjusted MBDA score, hereafter called the MBDA score. (Adjustment accounts for the effects of age, sex and adiposity1). MBDA scores (natural scale) and biomarker concentrations (log scale) were modeled using generalized estimating equations (GEE) that account for correlations between measurements from the same subject at multiple timepoints. Significance of MBDA score change or biomarker concentration change over time was determined by a likelihood ratio test of timepoints.Results:Of the 22 healthy subjects receiving the influenza virus vaccine, 14 (63.6%) were female, with mean (SD) age of 40.0 years (8.9). MBDA scores were low (<30), moderate (30-44) or high (>44) for 15 (68%), 6 (27%) and 1 (5%) subjects at baseline, and this distribution was stable over time (Figure 1). Overall, MBDA scores did not change significantly over time (p=0.48, Figure 2). Mean changes in MBDA score (95% CI) from baseline to weeks 1, 2 and 3 were 0.32 (-3.07, 3.71), 0.82 (-3.03, 4.67) and 2.86 (-1.10, 6.82), respectively (Figure 2); the week 3 value becomes 0.95 (-1.78, 3.68) if the week 3 outlier is removed. Among the 66 post-baseline measurements of change in MBDA score (Figure 2), 3 (5%) exceeded the 95% CI for change in MBDA score in this study (i.e., 14). When assessing the entire cohort across all timepoints, EGF was the only biomarker that demonstrated statistically significant change over time (p=5.6 x 10-7). At weeks 1, 2 and 3, the mean relative concentrations of EGF, compared with baseline, were 0.62 (0.52, 0.74), 0.86 (0.70, 1.06) and 0.62 (0.50, 0.76), respectively.Figure 1Figure 2Conclusion:Immunization of 22 healthy subjects with a quadrivalent influenza vaccine did not have a statistically significant effect on MBDA scores during a 3-week observation, and it had minimal effect on the component biomarkers.References:[1]Curtis et al.Rheumatology [Oxford]2018;58:874Disclosure of Interests:Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Lauren Lenz Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Megan Horton Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Darl Flake Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Eric Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead
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Raoufi, Ehsan, Bahar Bahramimeimandi, M. Salehi-Shadkami, Patcharida Chaosri, and M. R. Mozafari. "Methodical Design of Viral Vaccines Based on Avant-Garde Nanocarriers: A Multi-Domain Narrative Review." Biomedicines 9, no. 5 (May 6, 2021): 520. http://dx.doi.org/10.3390/biomedicines9050520.
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The current health crisis caused by coronavirus 2019 (COVID-19) and associated pathogens emphasize the urgent need for vaccine systems that can generate protective and long-lasting immune responses. Vaccination, employing peptides, nucleic acids, and other molecules, or using pathogen-based strategies, in fact, is one of the most potent approaches in the management of viral diseases. However, the vaccine candidate requires protection from degradation and precise delivery to the target cells. This can be achieved by employing different types of drug and vaccine delivery strategies, among which, nanotechnology-based systems seem to be more promising. This entry aims to provide insight into major aspects of vaccine design and formulation to address different diseases, including the recent outbreak of SARS-CoV-2. Special emphasis of this review is on the technical and practical aspects of vaccine construction and theranostic approaches to precisely target and localize the active compounds.
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Soldatou, Vasiliki, Anastasios Soldatos, and Theodoros Soldatos. "Examining Socioeconomic and Computational Aspects of Vaccine Pharmacovigilance." BioMed Research International 2019 (February 19, 2019): 1–15. http://dx.doi.org/10.1155/2019/6576483.
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Background. Vaccine pharmacovigilance relates to the detection of adverse events, their assessment, understanding, and prevention, and communication of their risk to the public. These activities can be tedious and long lasting for regulatory authority scientists and may be affected by community practices and public health policies. To better understand underlying challenges, we examined vaccine adverse event reports, assessed whether data-driven techniques can provide additional insight in safety characterization, and wondered on the impact of socioeconomic parameters. Methods. First, we integrated VAERS content with additional sources of drug and molecular data and examined reaction and outcome occurrence by using disproportionality metrics and enrichment analysis. Second, we reviewed social and behavioral determinants that may affect vaccine pharmacovigilance aspects. Results. We describe our experience in processing more than 607000 vaccine adverse event reports and report on the challenges to integrate more than 95500 VAERS medication narratives with structured information about drugs and other therapeutics or supplements. We found that only 12.6% of events were serious, while 8.97% referred to polypharmacy cases. Exacerbation of serious clinical patient outcomes was observed in 8.88% VAERS cases in which drugs may interact with vaccinations or with each other, regardless of vaccine activity interference. Furthermore, we characterized the symptoms reported in those cases and summarized reaction occurrence among vaccine-types. Last, we examine socioeconomic parameters and cost-management features, explore adverse event reporting trends, and highlight perspectives relating to the use and development of digital services, especially in the context of personalized and collaborative health-care. Conclusions. This work provides an informative review of VAERS, identifies challenges and limitations in the processing of vaccine adverse event data, and calls for the better understanding of the socioeconomic landscape pertaining vaccine safety concerns. We expect that adoption of computational techniques for integrated safety assessment and interpretation is key not only to pharmacovigilance practice but also to stakeholders from the entire healthcare system.
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Ramos, Laylaa, Joan K. Lunney, and Mercedes Gonzalez-Juarrero. "Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models." Disease Models & Mechanisms 13, no. 9 (September 1, 2020): dmm045740. http://dx.doi.org/10.1242/dmm.045740.
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ABSTRACTNeonatal and infant immunity differs from that of adults in both the innate and adaptive arms, which are critical contributors to immune-mediated clearance of infection and memory responses elicited during vaccination. The tuberculosis (TB) research community has openly admitted to a vacuum of knowledge about neonatal and infant immune responses to Mycobacterium tuberculosis (Mtb) infection, especially in the functional and phenotypic attributes of memory T cell responses elicited by the only available vaccine for TB, the Bacillus Calmette–Guérin (BCG) vaccine. Although BCG vaccination has variable efficacy in preventing pulmonary TB during adolescence and adulthood, 80% of endemic TB countries still administer BCG at birth because it has a good safety profile and protects children from severe forms of TB. As such, new vaccines must work in conjunction with BCG at birth and, thus, it is essential to understand how BCG shapes the immune system during the first months of life. However, many aspects of the neonatal and infant immune response elicited by vaccination with BCG remain unknown, as only a handful of studies have followed BCG responses in infants. Furthermore, most animal models currently used to study TB vaccine candidates rely on adult-aged animals. This presents unique challenges when transitioning to human trials in neonates or infants. In this Review, we focus on vaccine development in the field of TB and compare the relative utility of animal models used thus far to study neonatal and infant immunity. We encourage the development of neonatal animal models for TB, especially the use of pigs.
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Fonseca Zangirolamo, Amanda, Nathalia Covre da Silva, Fábio Morotti, and Marcelo Marcondes Seneda. "The impact of sanity on the fertility of cows submitted to reproductive biotechnics." Revista Acadêmica: Ciência Animal 15, Suppl 2 (August 29, 2017): 91. http://dx.doi.org/10.7213/academica.15.s02.2017.a09.
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The productivity in the herds is directly associated with reproduction. Thus, in order to achieve a better efficiency, the most varied reproductive biotechniques have been applied to the plants. Several factors have a direct influence on reproductive performance, including genetics, nutrition, zootechnical management, and sanitation. However, the sanity of the herd through the use of prophylactic measures against infectious agents is often neglected. In this context, particular attention should be paid to health programs, since 37-50% of gestational losses in the herd are consequences of infectious diseases of the reproductive tract caused by viral, bacterial or protozoan agents. Thus, this review will discuss the main advantages obtained with the use of reproductive biotechniques to increase fertility and the epidemiological aspects related to the diseases that cause reproductive failures in cows. Finally, we will also explain the importance of implementing sanitary programs with adequate management and vaccination of animals, to minimize economic losses related to reproductive diseases and, consequently, obtain higher pregnancy rates in the use of reproduction biotechnologies.
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Kanyiri, Caroline W., Kimathi Mark, and Livingstone Luboobi. "Mathematical Analysis of Influenza A Dynamics in the Emergence of Drug Resistance." Computational and Mathematical Methods in Medicine 2018 (August 29, 2018): 1–14. http://dx.doi.org/10.1155/2018/2434560.
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Every year, influenza causes high morbidity and mortality especially among the immunocompromised persons worldwide. The emergence of drug resistance has been a major challenge in curbing the spread of influenza. In this paper, a mathematical model is formulated and used to analyze the transmission dynamics of influenza A virus having incorporated the aspect of drug resistance. The qualitative analysis of the model is given in terms of the control reproduction number,Rc. The model equilibria are computed and stability analysis carried out. The model is found to exhibit backward bifurcation prompting the need to lowerRcto a critical valueRc∗for effective disease control. Sensitivity analysis results reveal that vaccine efficacy is the parameter with the most control over the spread of influenza. Numerical simulations reveal that despite vaccination reducing the reproduction number below unity, influenza still persists in the population. Hence, it is essential, in addition to vaccination, to apply other strategies to curb the spread of influenza.
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Priori, R., G. Pellegrino, S. Colafrancesco, C. Alessandri, F. Ceccarelli, M. DI Franco, V. Riccieri, et al. "POS1219 SARS-COV-2 VACCINE HESITANCY AMONG PATIENTS WITH RHEUMATIC AND MUSCULOSKELETAL DISEASES: A MESSAGE FOR RHEUMATOLOGISTS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 893.1–893. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2622.
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Background:Conflicting results have been published regarding the risk of infection with SARS-CoV-2 and development of severe COVID-19 among patients affected by rheumatic musculoskeletal diseases (RMDs). [1-4] Taking into account the lack of effective drugs to treat the COVID-19 and despite the burdensome and costly lockdown measures adopted to counteract the spread of SARS-CoV-2, effective and safe vaccines appear reasonably to be the best strategy for fighting the virus. [6] Before vaccines availability, several reports showed that a non-negligible proportion of subjects, among the general population or within specific categories, would have refused vaccination against COVID-19 once possible;[6, 7] data on vaccination hesitation among patients with RMD are not available yet.Objectives:This study aimed to evaluate the attitude of patients with RMDs to vaccination against SARS-CoV-2 and explore the factors which may influence it.Methods:During the first weeks of Europe vaccination campaign, we proposed an online survey to Italian adult patients with RMDs followed up in the Rheumatology Unit. All patients fulfilled the most recent classification criteria for each disease. HCs were recruited using a “best friend” system. The informed consent was collected for all participants. The questionnaires included the following items: demographic features, presence of comorbidities, educational level, and ongoing therapy. The individual’s perception of the COVID-19 vaccination, as well as the willingness to receive a COVID-19 vaccination with targeted questions was properly assessed.For the statistical analyses, Mann-Whitney and Chi-square tests were used. To account for baseline clinical differences among RMD-patients and controls, multivariable logistic regression analysis was used; covariates were selected according to a clinical criterion. The hypothesis that willingness for COVID-19 vaccine varied in specific subgroups of patients was tested using interaction terms at logistic regression analysis. All statistical tests were performed using the RStudio graphical interface and all tests were two-sided with a significance level set at p<0.05.Results:We provided an online survey to 830 adult RMD-patients and 370 healthy controls (HCs). Overall, 626 RMD-patients and 345 HCs completed the survey. Patients with RMDs were less willing to receive a COVID-19 vaccination compared to HCs (Odds Ratio (OR) 0.24, 95% CI 0.17 – 0.34, p<0.0001) despite they perceived themselves as at higher risk both to get infected (OR 11.3, 95% CI 8 – 15.9, p<0.0001) and develop a severe COVID-19 (OR 11.06, 95% CI 7.8 – 15.6, p<0.0001) and even if they had been vaccinated for influenza and pneumococcus more frequently than controls (OR 1.60 95% CI 1.18 – 2.16, p=0.002; OR 2.23, 95% CI 1.34 – 3.73, p=0.002). However, our results reveal that RMD-patients are more willing to change their minds if properly informed by the rheumatologist (OR 3.08, 95% CI 2.19 – 4.34, p<0.0001) in comparison to controls.Conclusion:The results of our study indicate for the first time that patients with RMDs are less willing to receive COVID-19 vaccination compared to the general population, despite perceiving themselves as at higher risk of getting infected with SARS-CoV-2 and develop severe COVID-19. However, our data underscored a meaningful aspect: patients with RMDs may change their attitude to COVID-19 vaccination if properly informed about risks and benefits by their trusted specialist.The results of this study encourage the entire rheumatologist community to become more committed to patient education, increasing their willingness to COVID-19 vaccine, which is the most promising strategy to protect them from the virus.References:1]Favalli EG et al. Arthritis Rheumatol, 2020[2]Fredi M, et al. Lancet Rheumatol, 2020.[3]Giardina F et al. Rheumatol Int 2021.[4]Pellegrino G et al. Clin Rheumatol 2020.[5]Frederiksen LSF, et al. Front Immunol, 2020.[6]La Vecchia C et al. Med Lav 2020.[7]Qiao S, et al. medRxiv 2020.Disclosure of Interests:None declared
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Pawłowski, Bogusław, Judyta Nowak, Barbara Borkowska, Daria Augustyniak, and Zuzanna Drulis-Kawa. "Body height and immune efficacy: testing body stature as a signal of biological quality." Proceedings of the Royal Society B: Biological Sciences 284, no. 1859 (July 19, 2017): 20171372. http://dx.doi.org/10.1098/rspb.2017.1372.
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According to the good genes hypothesis and energy allocation theory, human adult body height may reflect biological quality. An important aspect of this quality is immune system functioning (ISF). The aim of this study was to evaluate the relationship between ISF and body height in healthy people. The ISF was determined by several important innate (total complement and lysozyme activity, neutrophil function) and adaptive immune parameters (lymphocytes, IgA and IgG, and response to the flu vaccine). Overall, 96 males and 97 females were subjected to flu vaccination, and of these, 35 males and 34 females were subjected to tetanus. Blood samples were collected before and four weeks after vaccination. Immunomodulatory factors, participant's age, body fat, and free testosterone levels, were controlled. There was no association between body height and all analysed immune parameters for both sexes. That might suggest that in Western society, a women's preference for taller men is not related to ‘good genes for immune competence’. We propose the novel Immunity Priority Hypothesis that explains the lack of relationship between adult body stature and ISF. This hypothesis, however, does not contradict the signalling role of a man's body height as a morphological marker of biological quality.
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Desquesnes, Marc, Philippe Holzmuller, De-Hua Lai, Alan Dargantes, Zhao-Rong Lun, and Sathaporn Jittaplapong. "Trypanosoma evansiand Surra: A Review and Perspectives on Origin, History, Distribution, Taxonomy, Morphology, Hosts, and Pathogenic Effects." BioMed Research International 2013 (2013): 1–22. http://dx.doi.org/10.1155/2013/194176.
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Trypanosoma evansi, the agent of “surra,” is a salivarian trypanosome, originating from Africa. It is thought to derive fromTrypanosoma bruceiby deletion of the maxicircle kinetoplastic DNA (genetic material required for cyclical development in tsetse flies). It is mostly mechanically transmitted by tabanids and stomoxes, initially to camels, in sub-Saharan area. The disease spread from North Africa towards the Middle East, Turkey, India, up to 53° North in Russia, across all South-East Asia, down to Indonesia and the Philippines, and it was also introduced by the conquistadores into Latin America. It can affect a very large range of domestic and wild hosts including camelids, equines, cattle, buffaloes, sheep, goats, pigs, dogs and other carnivores, deer, gazelles, and elephants. It found a new large range of wild and domestic hosts in Latin America, including reservoirs (capybaras) and biological vectors (vampire bats). Surra is a major disease in camels, equines, and dogs, in which it can often be fatal in the absence of treatment, and exhibits nonspecific clinical signs (anaemia, loss of weight, abortion, and death), which are variable from one host and one place to another; however, its immunosuppressive effects interfering with intercurrent diseases or vaccination campaigns might be its most significant and questionable aspect.
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Mata, Elena, Aiala Salvador, Manoli Igartua, Rosa María Hernández, and José Luis Pedraz. "Malaria Vaccine Adjuvants: Latest Update and Challenges in Preclinical and Clinical Research." BioMed Research International 2013 (2013): 1–19. http://dx.doi.org/10.1155/2013/282913.
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There is no malaria vaccine currently available, and the most advanced candidate has recently reported a modest 30% efficacy against clinical malaria. Although many efforts have been dedicated to achieve this goal, the research was mainly directed to identify antigenic targets. Nevertheless, the latest progresses on understanding how immune system works and the data recovered from vaccination studies have conferred to the vaccine formulation its deserved relevance. Additionally to the antigen nature, the manner in which it is presented (delivery adjuvants) as well as the immunostimulatory effect of the formulation components (immunostimulants) modulates the immune response elicited. Protective immunity against malaria requires the induction of humoral, antibody-dependent cellular inhibition (ADCI) and effector and memory cell responses. This review summarizes the status of adjuvants that have been or are being employed in the malaria vaccine development, focusing on the pharmaceutical and immunological aspects, as well as on their immunization outcomings at clinical and preclinical stages.
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Huang, Sheng-Wen, Ching-Hui Tai, Judith M. Fonville, Chin-Hui Lin, Shih-Min Wang, Ching-Chung Liu, Ih-Jen Su, Derek J. Smith, and Jen-Ren Wang. "Mapping Enterovirus A71 Antigenic Determinants from Viral Evolution." Journal of Virology 89, no. 22 (September 2, 2015): 11500–11506. http://dx.doi.org/10.1128/jvi.02035-15.
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ABSTRACTHuman enterovirus A71 (EV-A71) belongs to theEnterovirus Aspecies in thePicornaviridaefamily. Several vaccines against EV-A71, a disease causing severe neurological complications or even death, are currently under development and being tested in clinical trials, and preventative vaccination programs are expected to start soon. To characterize the potential for antigenic change of EV-A71, we compared the sequences of two antigenically diverse genotype B4 and B5 strains of EV-A71 and identified substitutions at residues 98, 145, and 164 in the VP1 capsid protein as antigenic determinants. To examine the effects of these three substitutions on antigenicity, we constructed a series of recombinant viruses containing different mutation combinations at these three residues with a reverse genetics system and then investigated the molecular basis of antigenic changes with antigenic cartography. We found that a novel EV-A71 mutant, containing lysine, glutamine, and glutamic acid at the respective residues 98, 145, and 164 in the VP1 capsid protein, exhibited neutralization reduction against patients' antisera and substantially increased virus binding ability to human cells. These observations indicated that this low-neutralization-reactive EV-A71 VP1-98K/145Q/164E mutant potentially increases viral binding ability and that surveillance studies should look out for these mutants, which could compromise vaccine efficacy.IMPORTANCEEmerging and reemerging EV-A71 viruses can cause severe neurological etiology, primarily affecting children, especially around Asia-Pacific countries. We identified a set of mutations in EV-A71 that both reduced neutralization activity against humoral immunity in antisera of patients and healthy adults and greatly increased the viral binding ability to cells. These findings provide important insights for EV-A71 antigenic determinants and emphasize the importance of continuous surveillance, especially after EV-A71 vaccination programs begin.
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Lamouroux, David, Jan Nagler, Theo Geisel, and Stephan Eule. "Paradoxical effects of coupling infectious livestock populations and imposing transport restrictions." Proceedings of the Royal Society B: Biological Sciences 282, no. 1800 (February 7, 2015): 20142805. http://dx.doi.org/10.1098/rspb.2014.2805.
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Spatial heterogeneity of a host population of mobile agents has been shown to be a crucial determinant of many aspects of disease dynamics, ranging from the proliferation of diseases to their persistence and to vaccination strategies. In addition, the importance of regional and structural differences grows in our modern world. Little is known, though, about the consequences when traits of a disease vary regionally. In this paper, we study the effect of a spatially varying per capita infection rate on the behaviour of livestock diseases. We show that the prevalence of an infectious livestock disease in a community of animals can paradoxically decrease owing to transport connections to other communities in which the risk of infection is higher. We study the consequences for the design of livestock transportation restriction measures and establish exact criteria to discriminate those connections that increase the level of infection in the community from those that decrease it.
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DiMaio, Daniel. "Small size, big impact: how studies of small DNA tumour viruses revolutionized biology." Philosophical Transactions of the Royal Society B: Biological Sciences 374, no. 1773 (April 8, 2019): 20180300. http://dx.doi.org/10.1098/rstb.2018.0300.
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Intense study of three families of small tumour viruses with double-stranded DNA genomes, carried out over 50 years, has had a profound impact on biology. The polyomaviruses and papillomaviruses have circular DNA genomes of approximately 5000 and approximately 8000 base-pairs, respectively, and thus encode only a handful of proteins. Adenoviruses have a 32 000-base-pair linear DNA genome, still far smaller than the three billion-base-pair human genome. Members of all three virus families can transform cultured cells to tumorigenicity and cause tumours in experimental animals. Several human papillomaviruses (HPV) and at least one polyomavirus are oncogenic in humans. Early analysis of these viruses, particularly the polyomavirus SV40, led to the development of many powerful experimental tools, including restriction mapping, site-directed mutagenesis, gene transfer, genome-wide sequencing and recombinant DNA. These tools have since been refined and used to study cellular genes, revolutionizing our understanding of biology. These tools were also applied to the viruses themselves. Analysis of the virus life cycle and the effect of these viruses on cells yielded important new insights into many aspects of gene expression, DNA replication, cell biology and carcinogenesis. These studies have also led to vaccination strategies to prevent infection and cancer in humans. This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.
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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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Lambe, Teresa, Georgina Bowyer, and Katie J. Ewer. "A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?" Philosophical Transactions of the Royal Society B: Biological Sciences 372, no. 1721 (April 10, 2017): 20160295. http://dx.doi.org/10.1098/rstb.2016.0295.
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Sporadic outbreaks of Ebola virus infection have been documented since the mid-Seventies and viral exposure can lead to lethal haemorrhagic fever with case fatalities as high as 90%. There is now a comprehensive body of data from both ongoing and completed clinical trials assessing various vaccine strategies, which were rapidly advanced through clinical trials in response to the 2013–2016 Ebola virus disease (EVD) public health emergency. Careful consideration of immunogenicity post vaccination is essential but has been somewhat stifled because of the wide array of immunological assays and outputs that have been used in the numerous clinical trials. We discuss here the different aspects of the immune assays currently used in the Phase I clinical trials for Ebola virus vaccines, and draw comparisons across the immune outputs where possible; various trials have examined both cellular and humoral immunity in European and African cohorts. Assessment of the safety data, the immunological outputs and the ease of field deployment for the various vaccine modalities will help both the scientific community and policy-makers prioritize and potentially license vaccine candidates. If this can be achieved, the next outbreak of Ebola virus, or other emerging pathogen, can be more readily contained and will not have such widespread and devastating consequences. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.
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Calder, Philip C., and Samantha Kew. "The immune system: a target for functional foods?" British Journal of Nutrition 88, S2 (November 2002): S165—S176. http://dx.doi.org/10.1079/bjn2002682.
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The immune system acts to protect the host from infectious agents that exist in the environment (bacteria, viruses, fungi, parasites) and from other noxious insults. The immune system is constantly active, acting to discriminate ‘non-self’ from ‘self’. The immune system has two functional divisions: the innate and the acquired. Both components involve various blood-borne factors (complement, antibodies, cytokines) and cells. A number of methodologies exist to assess aspects of immune function; many of these rely upon studying cells in cultureex vivo. There are large inter-individual variations in many immune functions even among the healthy. Genetics, age, gender, smoking habits, habitual levels of exercise, alcohol consumption, diet, stage in the female menstrual cycle, stress, history of infections and vaccinations, and early life experiences are likely to be important contributors to the observed variation. While it is clear that individuals with immune responses significantly below ‘normal’ are more susceptible to infectious agents and exhibit increased infectious morbidity and mortality, it is not clear how the variation in immune function among healthy individuals relates to variation in susceptibility to infection. Nutrient status is an important factor contributing to immune competence: undernutrition impairs the immune system, suppressing immune functions that are fundamental to host protection. Undernutrition leading to impairment of immune function can be due to insufficient intake of energy and macronutrients and/or due to deficiencies in specific micronutrients. Often these occur in combination. Nutrients that have been demonstrated (in either animal or human studies) to be required for the immune system to function efficiently include essential amino acids, the essential fatty acid linoleic acid, vitamin A, folic acid, vitamin B6, vitamin B12, vitamin C, vitamin E, Zn, Cu, Fe and Se. Practically all forms of immunity may be affected by deficiencies in one or more of these nutrients. Animal and human studies have demonstrated that adding the deficient nutrient back to the diet can restore immune function and resistance to infection. Among the nutrients studied most in this regard are vitamin E and Zn. Increasing intakes of some nutrients above habitual and recommended levels can enhance some aspects of immune function. However, excess amounts of some nutrients also impair immune function. There is increasing evidence that probiotic bacteria improve host immune function. The effect of enhancing immune function on host resistance to infection in healthy individuals is not clear.
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Moeser, Adam J. "357 Early life factors shaping gut development and lifelong disease risk." Journal of Animal Science 98, Supplement_4 (November 3, 2020): 92. http://dx.doi.org/10.1093/jas/skaa278.168.
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Abstract The first 3–4 months of postnatal life represents a critical period in gastrointestinal (GI) development that shapes lifelong function and disease resistance. During this period, extensive maturation of the immune and nervous systems, and epithelial transport and barrier function, occurs. While some aspects of early life gut development are genetically “hard-wired,” the GI system exhibits a high degree of plasticity, and thus developmental trajectory and long-term function can be significantly modified during this period via host and environmental influences. Stress or adversity during early critical periods of development has been recognized as a significant risk factor for the later-life susceptibility to several GI and systemic chronic inflammatory and debilitating diseases in humans and animals, including functional bowel disorders characterized by dysmotility and neuroinflammation, but also disease associated with systemic inflammation, such as metabolic disorders (obesity and Type 2 diabetes) and neurobehavioral disorders including anxiety and depression. Moreover, early life stressors include routine management practices such as maternal separation and early weaning, social disruption, and early immune activation from disease or vaccination, and thus early life stress is common in animals. While the link between early life adversity and later life disease risk is well-established across species, the mechanisms that link early life stress, gut development and lifelong disease risk are poorly understood, and thus targeted management, therapeutic and nutritional strategies to reduce the negative impacts of early life stress are lacking. This goal of this presentation is to provide a biological framework for understanding how early life environmental and host factors such as stress and biological sex can alter the normal trajectory of GI development and disease risk throughout the lifespan. Ways in which changes in gut development might drive the risk for diseases important to many species, such as metabolic disease, functional/inflammatory bowel disorders and neurobehavioral disorders, will be discussed.
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Adashi, Eli Y., and Ivan Glenn Cohen. "CRISPR immunity: a case study for justified somatic genetic modification?" Journal of Medical Ethics, March 3, 2021, medethics—2020–106838. http://dx.doi.org/10.1136/medethics-2020-106838.
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The current SARS-CoV-2 pandemic has killed thousands across the world. SARS-CoV-2 is the latest but surely not the last such global pandemic we will face. The biomedical response to such pandemics includes treatment, vaccination, and so on. In this paper, though, we argue that it is time to consider an additional strategy: the somatic (non-heritable) enhancement of human immunity. We argue for this approach and consider bioethics objections we believe can be overcome.
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Su, Hongwei, Kan Lin, Divya Tiwari, Claire Healy, Carolina Trujillo, Yao Liu, Thomas R. Ioerger, Dirk Schnappinger, and Sabine Ehrt. "Genetic models of latent tuberculosis in mice reveal differential influence of adaptive immunity." Journal of Experimental Medicine 218, no. 9 (July 16, 2021). http://dx.doi.org/10.1084/jem.20210332.
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Studying latent Mycobacterium tuberculosis (Mtb) infection has been limited by the lack of a suitable mouse model. We discovered that transient depletion of biotin protein ligase (BPL) and thioredoxin reductase (TrxB2) results in latent infections during which Mtb cannot be detected but that relapse in a subset of mice. The immune requirements for Mtb control during latency, and the frequency of relapse, were strikingly different depending on how latency was established. TrxB2 depletion resulted in a latent infection that required adaptive immunity for control and reactivated with high frequency, whereas latent infection after BPL depletion was independent of adaptive immunity and rarely reactivated. We identified immune signatures of T cells indicative of relapse and demonstrated that BCG vaccination failed to protect mice from TB relapse. These reproducible genetic latency models allow investigation of the host immunological determinants that control the latent state and offer opportunities to evaluate therapeutic strategies in settings that mimic aspects of latency and TB relapse in humans.
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Novelli, Giuseppe, Michela Biancolella, Ruty Mehrian-Shai, Vito Luigi Colona, Anderson F. Brito, Nathan D. Grubaugh, Vasilis Vasiliou, Lucio Luzzatto, and Juergen K. V. Reichardt. "COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy." Human Genomics 15, no. 1 (May 10, 2021). http://dx.doi.org/10.1186/s40246-021-00326-3.
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AbstractCOVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents.
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Bellucci, Gianmarco, Virginia Rinaldi, Maria Chiara Buscarinu, Roberta Reniè, Rachele Bigi, Giulia Pellicciari, Emanuele Morena, et al. "Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?" Frontiers in Immunology 12 (September 27, 2021). http://dx.doi.org/10.3389/fimmu.2021.755333.
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Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host’s genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host’s response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.
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Littera, Roberto, Marcello Campagna, Silvia Deidda, Goffredo Angioni, Selene Cipri, Maurizio Melis, Davide Firinu, et al. "Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience." Frontiers in Immunology 11 (December 4, 2020). http://dx.doi.org/10.3389/fimmu.2020.605688.
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AimSARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome.Method and MaterialsWe recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies.ResultsMale sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8–8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7–220.6), Pc = 0.024].ConclusionThe data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.
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Bhavani, A. V. S. Ksheera, A. Lakshmi Usha, M. Kusama Kumari, and E. Radha Rani. "A Novel Technique for Intradermal Delivery of Drugs – Coated Polymeric Needles." Research Journal of Topical and Cosmetic Sciences, May 17, 2021, 25–31. http://dx.doi.org/10.52711/2321-5844.2021.00004.
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The barrier properties of the topmost layer of the skin, stratum corneum have significant limitations for successful systemic delivery of a wide range of therapeutic molecules, especially macromolecules and genetic material. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing through the stratum corneum and directly translocating protein drugs into the systematic circulation. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform technique has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therap. As an alternative to hypodermic needles, coated polymer microneedles (MNs) are able to deliver drugs to subcutaneous tissues after being inserted into the skin. The dip-coating process is a versatile, rapid fabricating method that can form coated MNs in a short time. However, it is still a challenge to fabricate coated MNs with homogeneous and precise drug doses in the dip-coating process. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. The clinical potential and future translation of MNs are also discussed.
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Toor, Jaspreet, Susy Echeverria-Londono, Xiang Li, Kaja Abbas, Emily D. Carter, Hannah E. Clapham, Andrew Clark, et al. "Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world." eLife 10 (July 13, 2021). http://dx.doi.org/10.7554/elife.67635.
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Background:Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000–2030 across 112 countries.Methods:Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios.Results:We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000–2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases.Conclusions:This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.Funding:VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium’s modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
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Biloivan, Oleksandr V., Angela Duerr, Julia Schwartz, Vasiliy Arefev, Oleksii Solodinkin, Borys Stegniy, and Anton Gerilovych. "Phylogenetic analysis of Ukrainian Bacillus anthracis strains from various sources." Online Journal of Public Health Informatics 11, no. 1 (May 30, 2019). http://dx.doi.org/10.5210/ojphi.v11i1.9768.
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ObjectiveDue to the lack of information about the phylogenetic origins of Ukrainian Bacillus anthracis strains,the goal of this work was to make phylogenetic analysis of Ukrainian isolates obtained from various sources (soil, clinical material from infected humans and animal products) for better understanding of phylogenetic origins of this pathogen in Ukraine and Eastern Europe.IntroductionAnthrax is a widely spread zoonotic disease with natural transmissive cycle involving wildlife, livestock and humans [1]. It is caused by Bacillus anthracis, a highly pathogenic gram-positive, spore-producing bacterium, which poses a serious threat to public and animal health due to its mortality both for animals and for humans [2, 3, 4]. The ability of B. anthracis spores to remain viable in soils for decades enables their isolation from freely accessible environment [5]. This unique feature to form highly resistant spores in the environment plays a major role in the ecology and evolution of this pathogen [6]. During the spore phase, evolution is greatly reduced in rate, which limits the amount of genetic diversity found among isolates of this species [1]. All these factors demonstrate the need for reliable anthrax diagnosis and trace-back methods. This comprises bio forensic capabilities including state-of-the-art methods for accurate genotyping of B. anthracis strains.Methods23 thermolysates of B. anthracis broth cultures isolated from various sources (vesicles from eleven different people infected with cutaneous anthrax when disease’s sporadic outbreaks were detected in Ukraine in 1963-2002, as well as two samples from sheep wool, and eight soil samples) were obtained from the Central Epidemiological Station (Kyiv, Ukraine), as well as from I.I. Mechnikov Ukrainian Scientific and Research Anti-plaque Institute (Odessa, Ukraine). These anthrax cultures were confirmed with classical microbiological methods (microscopy, cultivation on solid and liquid media), “string of pearls” reaction, and using bioassay on living white mice (the mortality was observed two days after subcutaneous injection of 0,2-0,5 ml of cells’ suspension). All these tests were carried out at the institutions where samples were obtained. Besides, one B. anthracis isolate was cultivated from soil sample of an animal grave site nearby Koviagy village, Valky district, Kharkiv region. All samples were analyzed at the Bundeswehr Institute of Microbiology (Munich, Germany). To confirm the presence of the anthrax genome and plasmids, we isolated genomic DNA (gDNA) from thermolysates and studied the presence of the genomic marker dhp61 as well as the plasmid specific marker pagA (pXO1) and capC (pXO2) using qPCR. Quality of the isolated gDNA was tested using the Agilent bioanalyzer. To characterize regional and global phylogeographic patterns of these strains, canonical Single Nucleotide Polymorphisms analysis (canSNP) was conducted using high resolution melt (HRM). Three thermolysates of broth cultures isolated and soil sample isolated from animal grave site in Kharkiv region were analyzed using NewSeq Full genome sequencing.ResultsB. anthracis chromosomal DNA-marker dhp61 as well as pXO1 marker pagA and pXO2 plasmid marker capC could be detected in all thermolysates. However, the soil isolate from the Koviagy grave site was positive for dhp61 but contained only the pXO1 plasmid. The Bioanalyzer assay revealed that only 6 out of the 23 thermolysates had good enough DNA quality to be sequenced. So far only genomes of thermolysates of soil samples from Mykolaiv and Sumy regions, the thermolysate of sick patient's vesicle from Kherson region as well as the soil sample from the animal grave site in Kharkiv region have been sequenced. For the residual 3 thermolysates the full genome analysis is still in progress. The sequencing results showed that the B. anthracis strain isolated from Mykolaiv soil sample belongs to the Vollum linage group and other thermolysates from Sumy and Kherson regions are closely clustering with isolates from Japan. Thus, human isolate from Kherson region is clustering with the Japanese isolate BA104 which was obtained from pig during sporadic anthrax incident in 1982 and soil isolate from Sumy region is clustering with the BA 103 isolate which was obtained from beef cattle in Japan in 1991. In contrast, we analyzed the genomic sequence of the pXO2-negative isolate from grave site in Kharkiv region using BioNumerics software and found that it has high similarity to STI strain.ConclusionsThe infrequent sporadic occurrence of anthrax in the country of Ukraine is likely caused by a heterogeneous population of B. anthracis. The found STI strain in the grave site of Kharkiv region is probably an environmental recovery of the Russian anthrax live vaccine which was commonly used for vaccination of animals in the former Soviet Union The sequencing result of the soil isolate from Mykolaiv region indicates the occurrence of another canSNP group, the Vollum group, which is quite untypical for Ukraine. The latter is mainly prevalent in the Asian regions (namely Pakistan) and therefore might have been introduced to Ukraine over the silk road. Other two thermolysates from Sumy and Kherson regions also showed unexpected results clustering with Japanese isolates. The further research of Ukrainian B. anthracis isolates will allow us to expand our knowledge about the population structure and evolution of anthrax in Ukraine.References1. Van Ert MN, Easterday WR, Huynh LY, Okinaka RT, Hugh-Jones ME, Ravel J, et al. (2007) Global Genetic Population Structure of Bacillus anthracis. PLoS ONE 2(5);2. Freidlander, A. M. 1997. Anthrax, p. 467–478. In F. R. Sidell, E. T. Takafuji, and D. R. Franz (ed.), Medical aspects of chemical and biological warfare. Office of the Surgeon General, Washington, D.C.3. Hoffmaster AR, Fitzgerald CC, Ribot E, Mayer LW, Popovic T (2002) Molecular subtyping of Bacillus anthracis and the 2001 bioterrorism-associated anthrax outbreak, United States. Emerg Infect Dis 8: 1111–1116.4. Keim P, Van Ert MN, Pearson T, Vogler AJ, Huynh LY, et al. (2004) Anthrax molecular epidemiology and forensics: using the appropriate marker for different evolutionary scales. Infect Genet Evol 4: 205–213.5. Eitzen, E. M. 1997. Use of biological weapons, p. 437–450. In F. R. Sidell, E. T. Takafuji, and D. R. Franz (ed.), Medical aspects of chemical and biological warfare. Office of the Surgeon General, Washington, D.C.6. Biloivan O, Duerr A, Schwarz J, Grass G, Arefiev V, Solodiankin O, Stegniy B, Gerilovych A (2018) Phylogenetic analysis of Ukrainian Bacillus anthracis strains. Third Annual BTRP Ukraine Regional One Health Research Symposium, abstract directory: 122.
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Mazzocco, Giovanni, Iga Niemiec, Alexander Myronov, Piotr Skoczylas, Jan Kaczmarczyk, Anna Sanecka-Duin, Katarzyna Gruba, et al. "AI Aided Design of Epitope-Based Vaccine for the Induction of Cellular Immune Responses Against SARS-CoV-2." Frontiers in Genetics 12 (March 25, 2021). http://dx.doi.org/10.3389/fgene.2021.602196.
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The heavy burden imposed by the COVID-19 pandemic on our society triggered the race toward the development of therapies or preventive strategies. Among these, antibodies and vaccines are particularly attractive because of their high specificity, low probability of drug-drug interaction, and potentially long-standing protective effects. While the threat at hand justifies the pace of research, the implementation of therapeutic strategies cannot be exempted from safety considerations. There are several potential adverse events reported after the vaccination or antibody therapy, but two are of utmost importance: antibody-dependent enhancement (ADE) and cytokine storm syndrome (CSS). On the other hand, the depletion or exhaustion of T-cells has been reported to be associated with worse prognosis in COVID-19 patients. This observation suggests a potential role of vaccines eliciting cellular immunity, which might simultaneously limit the risk of ADE and CSS. Such risk was proposed to be associated with FcR-induced activation of proinflammatory macrophages (M1) by Fu et al. (2020) and Iwasaki and Yang (2020). All aspects of the newly developed vaccine (including the route of administration, delivery system, and adjuvant selection) may affect its effectiveness and safety. In this work we use a novel in silico approach (based on AI and bioinformatics methods) developed to support the design of epitope-based vaccines. We evaluated the capabilities of our method for predicting the immunogenicity of epitopes. Next, the results of our approach were compared with other vaccine-design strategies reported in the literature. The risk of immuno-toxicity was also assessed. The analysis of epitope conservation among other Coronaviridae was carried out in order to facilitate the selection of peptides shared across different SARS-CoV-2 strains and which might be conserved in emerging zootic coronavirus strains. Finally, the potential applicability of the selected epitopes for the development of a vaccine eliciting cellular immunity for COVID-19 was discussed, highlighting the benefits and challenges of such an approach.
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Sahu, Tanmaya Kumar, Anoop Kishor Singh Gurjar, Prabina Kumar Meher, Cini Varghese, Sudeep Marwaha, Govind Pratap Rao, Anil Rai, et al. "Computational insights into RNAi-based therapeutics for foot and mouth disease of Bos taurus." Scientific Reports 10, no. 1 (December 2020). http://dx.doi.org/10.1038/s41598-020-78541-6.
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AbstractFoot-and-mouth disease (FMD) endangers a large number of livestock populations across the globe being a highly contagious viral infection in wild and domestic cloven-hoofed animals. It adversely affects the socioeconomic status of millions of households. Vaccination has been used to protect animals against FMD virus (FMDV) to some extent but the effectiveness of available vaccines has been decreased due to high genetic variability in the FMDV genome. Another key aspect that the current vaccines are not favored is they do not provide the ability to differentiate between infected and vaccinated animals. Thus, RNA interference (RNAi) being a potential strategy to control virus replication, has opened up a new avenue for controlling the viral transmission. Hence, an attempt has been made here to establish the role of RNAi in therapeutic developments for FMD by computationally identifying (i) microRNA (miRNA) targets in FMDV using target prediction algorithms, (ii) targetable genomic regions in FMDV based on their dissimilarity with the host genome and, (iii) plausible anti-FMDV miRNA-like simulated nucleotide sequences (SNSs). The results revealed 12 mature host miRNAs that have 284 targets in 98 distinct FMDV genomic sequences. Wet-lab validation for anti-FMDV properties of 8 host miRNAs was carried out and all were observed to confer variable magnitude of antiviral effect. In addition, 14 miRBase miRNAs were found with better target accessibility in FMDV than that of Bostaurus. Further, 8 putative targetable regions having sense strand properties of siRNAs were identified on FMDV genes that are highly dissimilar with the host genome. A total of 16 SNSs having > 90% identity with mature miRNAs were also identified that have targets in FMDV genes. The information generated from this study is populated at http://bioinformatics.iasri.res.in/fmdisc/ to cater the needs of biologists, veterinarians and animal scientists working on FMD.
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Sanches, Marina Pinto, Sávio Matheus Reis de Carvalho, Cristiane Coelho Costa, Douglas Marinho De Abreu, Daiana Maria Do Nascimento, Willker Jhonatan De Jesus, Gerson Tavares Pessoa, and Jefferson Rodrigues Araújo. "Pectus carinatum in a Cat." Acta Scientiae Veterinariae 47 (September 27, 2019). http://dx.doi.org/10.22456/1679-9216.95873.
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Background: Pectus are congenital sternal deformities considered rare in small animals, and they are divided into two types. Pectus excavatum causes a concave aspect in the ventral portion of the animal’s thorax, which is known as “funnel chest,” while pectus carinatum produces a convex appearance and is therefore called “pigeon chest.” The etiology of these anomalies has not yet been fully elucidated, but it is assumed that there is genetic involvement. The diagnosis is based on clinical examination and is confirmed by thoracic radiography. This report describes a case of pectus carinatum in a one-month-old domestic cat.Case: An unspayed female domestic cat, about one month old, weighing 0.1 kg, was admitted to the Veterinary Hospital of the Federal University of Piauí (UFPI). When her history was taken, her owner reported that he had rescued the animal the previous day and noticed that showed difficulty breathing, so naturally worming and vaccination were not reported. Upon physical examination, the patient showed an abdominal breathing pattern, severe dyspnea, pale mucosa, nasal discharge, apathy, poor nutritional status (body score 1), signs of apparent dehydration and a temperature of 38.5ºC. Palpation revealed increased volume in the thoracic region. X-rays were ordered due to suspicion of diaphragmatic injury. The chest X-ray report indicated ventral segment displacement of the 4th to the 8th sternebra, with accommodation of the cardiac silhouette in the right lateral, left lateral and dorsoventral projections, suggesting pectus carinatum. Pulmonary radiodensity was also augmented, with greater intensity in the right middle lobe, an alveolar pattern, radiographic signs suggestive of an infectious process (pneumonia), and pulmonary hyperinflation. A qualitative analysis revealed cardiac silhouette whose dimensions showed no radiographic evidence of alterations at the moment of the examination. The diaphragmatic dome was intact. Normally aerated thoracic trachea, with preserved dorsoventral diameter.Discussion: Although deformities of the chest wall are infrequent and cases of pectus carinatum (PC) have rarely been published in veterinary medicine, reports of pectus excavatum (PE) in both dogs and cats are more easily found. Therefore, epidemiological data on PC are unknown, and moreover, most veterinary clinicians and surgeons are unaware of this anomaly. In the case of this kitten, pectus carinatum was diagnosed based on imaging tests allied to a clinical evaluation. The pathophysiology of the deformity has not yet been fully elucidated. In a case reported in a Shih Tzu dog, it was pointed out that one of its siblings had died at birth, and that the parents had no kinship and no congenital or hereditary abnormality. In another case of a five-month-old miniature pinscher, born from a consanguineous gestation, several anomalies were observed, in addition to pectus carinatum, such as dental malocclusion, poor limb alignment and locomotion difficulty, bilateral cryptorchidism and umbilical hernia. Because it was a rescue dog, the appearance of the anomaly could not be attributed to consanguinity in the reported case. No other anomalies were observed. Therefore, it is worth emphasizing that the earlier the diagnosis the better the animal’s prognosis. However, further studies are needed in order to clarify the etiology, determine possibilities of intervention and devise treatments.