A5056393456- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- Viral Infections and Immunology Research
- Immune Cell Function and Interaction
- Leprosy Research and Treatment
- SARS-CoV-2 detection and testing
- Mycobacterium research and diagnosis
- vaccines and immunoinformatics approaches
- Tuberculosis Research and Epidemiology
- Influenza Virus Research Studies
- HIV Research and Treatment
- CAR-T cell therapy research
- Viral Infections and Outbreaks Research
- T-cell and B-cell Immunology
- Nuclear Receptors and Signaling
- Respiratory viral infections research
- Infectious Diseases and Tuberculosis
- Viral Infections and Vectors
- Hepatitis C virus research
- Long-Term Effects of COVID-19
- Chemokine receptors and signaling
Vanderbilt University Medical Center
2017-2025
Nashville Oncology Associates
2021-2024
Vanderbilt University
2021-2024
Vanderbilt Health
2022
VA Tennessee Valley Healthcare System
2019-2022
Lepra Society
2012-2020
Bipar
2019-2020
University of Hyderabad
2020
The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome 2 (SARS-CoV-2), a major threat to global health1 and the medical countermeasures available so far are limited2,3. Moreover, we currently lack thorough understanding mechanisms humoral immunity SARS-CoV-24. Here analyse large panel human monoclonal antibodies that target spike (S) glycoprotein5, identify several exhibit potent neutralizing activity fully block receptor-binding...
Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and a major contributor to neutralizing antibody responses elicited by infection. Here, we describe deep mutational scanning method map how all amino-acid mutations in RBD affect binding apply this 10 human monoclonal antibodies. The escape cluster on several surfaces of that broadly correspond structurally defined epitopes. However, even antibodies same surface often have distinct...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera from recipients of BNT162b2 mRNA vaccine, we report impact on neutralization a panel authentic including B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes isogenic...
A wide spectrum of clinical manifestations has become a hallmark the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although immunological underpinnings diverse disease outcomes remain to be defined. We performed detailed characterization B cell responses through high-dimensional flow cytometry reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks extrafollicular activation shared...
Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and make a major contribution to neutralizing antibody response elicited by infection. Here, we describe deep mutational scanning method map how all amino-acid mutations in RBD affect binding, apply this 10 human monoclonal antibodies. The escape cluster on several surfaces of that broadly correspond structurally defined epitopes. However, even antibodies same surface often have...
Cancer vaccines targeting patient-specific neoantigens have emerged as a promising strategy for improving responses to immune checkpoint blockade. However, neoantigenic peptides are poorly immunogenic and inept at stimulating CD8+ T cell responses, motivating need new vaccine technologies that enhance their immunogenicity. The stimulator of interferon genes (STING) pathway is an endogenous mechanism by which the innate system generates immunological context priming mobilizing...
Tissue-resident memory T cells (TRM) patrol nonlymphoid organs and provide superior protection against pathogens that commonly infect mucosal barrier tissues, such as the lungs, intestine, liver, skin. Thus, there is a need for vaccine technologies can induce robust, protective TRM response in these tissues. Nanoparticle (NP) vaccines offer important advantages over conventional vaccines; however, has been minimal investigation into design of NP-based eliciting responses. Here, we describe...
Abstract Vaccination with vaccinia virus (VACV) elicits heterotypic immunity to smallpox, monkeypox, and mousepox, the mechanistic basis for which is poorly understood. It generally assumed that arises from presentation of a wide array VACV-derived, CD8 + T cell epitopes share homology other poxviruses. Herein this assumption was tested using large panel VACV-derived peptides presented by HLA-B*07:02 (B7.2) molecules in mousepox/ectromelia (ECTV)-infection, B7.2 transgenic mouse model. Most...
Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases, well healthy individuals. Here we identify 37 clonotypes memory B cells from convalescent survivors severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or plasmablasts an individual after vaccination with mRNA-encoded spike protein. We 29 including recognizing the receptor-binding domain (RBD) protein S1...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic infecting more than 106 million people and causing 2.3 deaths. The rapid deployment of antibody-based countermeasures provided hope for curtailing disease ending
The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family viruses. From a recovered SARS-CoV donor sample, we identify characterize panel six monoclonal antibodies that cross-react with CoV spike (S) proteins from highly pathogenic SARS-CoV-2, demonstrate spectrum reactivity other CoVs. Epitope mapping reveals these recognize multiple epitopes on...
Preexisting immunity against seasonal coronaviruses (CoVs) represents an important variable in predicting antibody responses and disease severity to severe acute respiratory syndrome CoV-2 (SARS-CoV-2) infections. We used electron microscopy-based polyclonal epitope mapping (EMPEM) characterize the specificities β-CoV spike proteins prepandemic (PP) sera or SARS-CoV-2 convalescent (SC) sera. observed that most PP had antibodies specific human CoVs (HCoVs) OC43 HKU1 while SC showed reactivity...
RNA-based vaccines against SARS-CoV-2 have proven critical to limiting COVID-19 disease severity and spread. Cellular mechanisms driving antigen-specific responses these vaccines, however, remain uncertain. Here we identify characterize cells antibody the RNA vaccine BNT162b2 using multiple single-cell technologies for in depth analysis of longitudinal samples from a cohort healthy participants. Mass cytometry unbiased machine learning pinpoint an expanding, population memory CD4+ CD8+ T...
Summary Most human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with cellular receptor angiotensin-converting enzyme 2. We describe a panel of mAbs binding to diverse epitopes on N-terminal (NTD) S from convalescent donors found minority these possessed activity. Two (COV2-2676 COV2-2489) inhibited infection authentic recombinant VSV/SARS-CoV-2 viruses. mapped their by alanine-scanning mutagenesis...
The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates virion surface and mediates cell binding entry. Most SARS-CoV-2 antibodies target receptor-binding domain or a single dominant epitope ("supersite") N-terminal (NTD). Using B technology called linking receptor antigen specificity through sequencing (LIBRA-Seq), we isolated large panel of NTD-reactive SARS-CoV-2–neutralizing from an...
The COVID-19 pandemic is a major threat to global health for which there are only limited medical countermeasures, and we lack thorough understanding of mechanisms humoral immunity 1,2 . From panel monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein isolated from B cells infected subjects, identified several mAbs that exhibited potent neutralizing activity with IC 50 values as low 0.9 or 15 ng/mL in pseudovirus wild-type ( wt ) SARS-CoV-2 neutralization tests, respectively....
Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused global pandemic with millions infections hundreds thousands deaths date 1,2 . In response, we used rapid antibody discovery platform isolate human monoclonal antibodies (mAbs) against the spike (S) protein. We stratify these mAbs into five classes based on their reactivity subdomains S protein as well...
In recent years, genome wide association studies have discovered a large number of gene loci that play functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control intracellular bacteria M. leprae is modulated by NOD2-mediated signaling Th1 responses. this study, we investigated 211 clinically classified patients 230 ethnically matched controls Indian population genotyping four variants NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G),...
Broadly reactive antibodies targeting the influenza A virus hemagglutinin (HA) head domain are thought to be rare and require extensive somatic mutations or unusual structural features achieve breadth against divergent HA subtypes. Here we describe common genetic of protective human from several individuals recognizing trimer interface (TI) head, a recently identified site vulnerability. We examined sequence TI-reactive antibodies, determined crystal structures for TI antibody–antigen...