A5042297045- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Influenza Virus Research Studies
- Immunotherapy and Immune Responses
- Animal Disease Management and Epidemiology
- Tuberculosis Research and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Microbial infections and disease research
- Mycobacterium research and diagnosis
- Research on Leishmaniasis Studies
- T-cell and B-cell Immunology
- Congenital Anomalies and Fetal Surgery
- Pneumocystis jirovecii pneumonia detection and treatment
- Parasitic infections in humans and animals
- Hepatitis C virus research
- Viral Infections and Immunology Research
- Respiratory viral infections research
- Viral Infectious Diseases and Gene Expression in Insects
- Biochemical and Molecular Research
- Parasitic Infections and Diagnostics
- Virus-based gene therapy research
- Bacterial Infections and Vaccines
- Malaria Research and Control
Providence College
2014-2024
EpiVax (United States)
2015-2024
University of Rhode Island
2012-2017
Institute for Medical Informatics and Biostatistics
2012-2015
Universidad Peruana Cayetano Heredia
2009-2013
Farvet (Peru)
2013
Response Technologies (United States)
2002
Computational vaccine design, also known as computational vaccinology, encompasses epitope mapping, antigen selection and immunogen design using tools. The iVAX toolkit is an integrated set of tools that has been in development since 1998 by De Groot Martin. It comprises a suite immunoinformatics algorithms for triaging candidate antigens, selecting immunogenic conserved T cell epitopes, eliminating regulatory optimizing antigens immunogenicity protection against disease. applied to programs...
Advances in the field of T cell immunology have contributed to understanding that cross-reactivity is an intrinsic characteristic receptor (TCR), and each TCR can potentially interact with many different epitopes. To better define potential for between epitopes derived from human genome, microbiome, pathogens, we developed a new immunoinformatics tool, JanusMatrix, represents extension validated epitope mapping EpiMatrix. Initial explorations, summarized this synopsis, uncovered what appear...
In silico immunogenicity risk assessment has been an important step in the development path for many biologic therapeutics, including monoclonal antibodies. Even if source of a given is 'fully human', T cell epitopes that are contained sequences may activate immune system, enabling anti-drug antibodies can reduce drug efficacy and contribute to adverse events. Computational tools identify from primary amino acid have used assess immunogenic potential therapeutic candidates several decades....
Hypothesis While conventional in silico immunogenicity risk assessments focus on measuring based the potential of therapeutic proteins to be processed and presented by a global population-wide set human leukocyte antigen (HLA) alleles T cells, future refinements might adjust for HLA allele frequencies different geographic regions or populations, as well individuals those populations. Adjustment distribution may reveal patterns that are specific population groups individuals, which current...
ABSTRACT Despite high quality standards and continual process improvements in manufacturing, host cell protein (HCP) impurities remain a substantial risk for biological products. Even at low levels, residual HCPs can induce detrimental immune response compromising the safety efficacy of biologic. Consequently, advanced‐stage clinical trials have been cancelled due to identification antibodies against HCPs. To enable earlier rapid assessment risks Chinese Hamster Ovary (CHO)‐based production...
Abstract Natural and vaccine-induced SARS-CoV-2 immunity in humans has been described but correlates of protection are not yet defined. T cells support the antibody response, clear virus-infected cells, may be required to block transmission. In this study, we identified peptide epitopes associated with T-cell immunity. Using immunoinformatic methods, from spike, membrane, envelope were selected for maximal HLA-binding potential, coverage HLA diversity, circulating virus, minimal potential...
Avian-origin H7N9 influenza is a novel A virus (IAV) that emerged in humans China 2013. Using immunoinformatics tools, we identified several T cell epitopes with receptor (TCR)-facing residues identical to those of multiple from human proteins. We hypothesized host tolerance these peptides may impair helper response and contribute the low titer, weak hemagglutination inhibiting (HI) antibody responses diminished seroconversion rates have been observed infections vaccine trials. found...
High strain sequence variability, interference with innate immune mechanisms, and epitope deletion are all examples of strategies that pathogens have evolved to subvert host defenses. To this list we would add another strategy: camouflage. Pathogens whose sequences cross-conserved multiple human proteins at the TCR-facing residues may be exploiting "ignorance tolerance," which mechanisms by mature T cells avoid responses self-antigens. By adopting amino acid configurations recognized...
Swine influenza is a highly contagious respiratory viral infection in pigs that responsible for significant financial losses to pig farmers annually. Current measures protect herds from include: inactivated whole-virus vaccines, subunit and alpha replicon-based vaccines. As true vaccines humans, these strategies do not provide broad protection against the diverse strains of A virus (IAV) currently circulating U.S. swine. Improved approaches developing swine are needed. Here, we used...
SUMMARY Introduction . Evaluation of Leishmania drug susceptibility depends on in vitro Sb V assays, which are labour-intensive and may give a biased view the true parasite resistance. Molecular markers urgently needed to improve simplify monitoring -resistance. We analysed here gene expression profile 21 L. braziliensis clinical isolates defined as -resistant -sensitive, order identify potential resistance markers. Methods The differential 13 genes involved metabolism, oxidative stress or...
Immune recognition of foreign proteins by T cells hinges on the formation a ternary complex sandwiching constituent peptide protein between major histocompatibility (MHC) molecule and cell receptor (TCR). Viruses have evolved means "camouflaging" themselves, avoiding immune reducing MHC and/or TCR binding their peptides. Computer-driven epitope mapping tools been used to evaluate degree which particular viruses this response, but most such analyses focus MHC-facing 'agretopes'. Here we set...
Over many years, recombinant protein biologics developers have addressed product immunogenicity with a focus on the active pharmaceutical ingredient. Recently, immune responses to native host cell proteins (HCP) gained attention, as they too may an effect response formulated drug, namely diminished drug safety and efficacy. The recent suspension of two clinical trials due presence antibodies Chinese Hamster Ovary (CHO) HCPs in subjects treated biologic clearly reveals serious concern...
Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance increasing. First second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani GP63 peptides using immunoinformatics tools test their immunogenicity in vitro. amino acid sequence [GenBank accession: ACT31401] screened EpiMatrix algorithm putative T cell epitopes that would bind most common HLA...
Porcine circovirus type 2 (PCV2) has one of the highest evolutionary rates among DNA viruses. Traditionally, PCV2 vaccines have been based on 2a genotype as this was first discovered. Today, eight genotypes viruses identified, and, taken together with rapid rate, propensity to recombine, and high rate vaccination, further variation in is expected. For these reasons, there a growing genetic gap between available field strains. When selecting vaccines, it important consider that contain T cell...
T cell epitope prediction tools and associated vaccine design algorithms have accelerated the development of vaccines for humans. Predictive swine other food animals are not as well developed, primarily because data required to develop lacking. Here, we overcome a lack construct predictors by systematically leveraging available human information. Applying "pocket profile method", use sequence structural similarities in binding pockets major histocompatibility complex proteins infer Swine...
The RTS,S/AS01 malaria vaccine will undergo a pilot vaccination study in sub-Saharan Africa beginning 2019. Phase III trials reported an efficacy of 28.3% (children 5-17 months) and 18.3% (infants 6-12 weeks), with substantial variability across sites. We postulated that the relatively low RTS,S sites may be due to lack T-cell epitopes antigen, HLA distribution vaccinated population, and/or 'immune camouflage', immune escape mechanism. To examine these hypotheses, we used immunoinformatics...
The in silico prediction of T cell epitopes within any peptide or biologic drug candidate serves as an important first step for assessing immunogenicity. bind human leukocyte antigen (HLA) by a well-characterized interaction amino acid side chains and pockets the HLA molecule binding groove. Immunoinformatics tools, such EpiMatrix algorithm, have been developed to screen natural sequences peptides that will HLA. In addition commonly occurring synthetic impurities, unnatural acids (UAA) are...
Zika virus (ZIKV) is a flavivirus primarily transmitted by Aedes species mosquitoes, first discovered in Africa 1947, that disseminated through Southeast Asia and the Pacific Islands 2000s. The ZIKV infections Americas were identified 2014, exploded populations Brazil other countries 2015/16. infection during pregnancy can cause severe brain eye defects offspring, adults has been associated with higher risks of Guillain-Barré syndrome. We initiated study to describe natural history (the...
Pyrazinamidase of Mycobacterium tuberculosis catalyzes the conversion pyrazinamide to active molecule pyrazinoic acid. Reduction pyrazinamidase activity results in a level resistance. Previous studies have suggested that has metal-binding site and divalent metal cofactor is required for activity. To determine effect metals on pyrazinamidase, recombinant wild-type corresponding H37Rv pyrazinamide-susceptible reference strain was expressed Escherichia coli with without carboxy terminal....