Georgia D. Tomaras
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- HIV/AIDS Research and Interventions
- Herpesvirus Infections and Treatments
- Hepatitis C virus research
- Virology and Viral Diseases
- SARS-CoV-2 and COVID-19 Research
- Cytomegalovirus and herpesvirus research
- Blood groups and transfusion
- Immunodeficiency and Autoimmune Disorders
- Malaria Research and Control
- Virus-based gene therapy research
- Immune responses and vaccinations
- Complement system in diseases
- Hepatitis B Virus Studies
- interferon and immune responses
- RNA Interference and Gene Delivery
- COVID-19 Clinical Research Studies
- Vaccine Coverage and Hesitancy
- Glycosylation and Glycoproteins Research
Duke Medical Center
2016-2025
Duke University
2016-2025
International Vaccine Institute
2008-2025
Duke University Hospital
2014-2025
Center for Human Genetics
2021-2025
University of Washington
2023
Duke Institute for Health Innovation
2014-2023
National Cancer Institute
2013-2020
Center for Cancer Research
2020
Délégation Paris 7
2019
The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating molecular basis transmission and designing effective vaccines. Here, we developed a mathematical model random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects acute (clade B) infection. Viral genes evolving individual...
In the RV144 trial, estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed case–control analysis to identify antibody and cellular immune correlates infection risk.
A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment transmission through establishment latent pool HIV-1-infected cells. critical time study initial transmitted/founder is eclipse phase HIV-1 infection (time first appearance plasma virus), but, date, this period has been logistically difficult analyze. To probe B-cell immediately following transmission, we have determined envelope-specific antibody autologous and...
A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested efficacy DNA prime-recombinant adenovirus 5 boost (DNA/rAd5) regimen in persons at increased risk HIV-1 United States.
A V1-V2 IgG3 response to HIV correlates with a decreased risk of HIV-1 infection and is one vaccine-induced humoral that higher in clinical trial showing vaccine efficacy compared nonefficacy.
V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known neutralizing has proven elusive, the induction with such specificity is important goal for vaccine development. A critical question which immunogens formulations might be used to trigger drive development memory B cell precursors specificity. In this paper we identified a clonal lineage four (CH01 CH04) from African HIV-1-infected broad...
Analysis of correlates risk infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas Env-specific IgA responses directly risk. In secondary analysis, antibody-dependent cellular cytotoxicity (ADCC) was another inverse correlate but only presence low antibodies. Thus, we investigated hypothesis could attenuate protective effect through competition for same Env binding sites. We...
The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. secondary immune correlate analysis demonstrated that the combination low plasma anti-HIV-1 Env IgA antibodies and high levels antibody-dependent cellular cytotoxicity (ADCC) inversely with infection risk. One hypothesis is observed protection in partially due to ADCC-mediating antibodies. We found majority (73 90%) a representative group vaccinees displayed ADCC activity, usually (96.2%) blocked by...
ABSTRACT Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist design of vaccines to elicit similar responses. Here, we investigated activities a panel 24 broadly plasmas from subtype B- and C-infected donors using series complementary mapping methods, focusing mostly on JR-FL as prototype B primary isolate. Adsorption with gp120 immobilized beads revealed an often...
To determine the spectrum of antiviral antibodies in HIV-1-infected individuals whom viral replication is spontaneously undetectable, termed HIV controllers (HICs).Multicenter French trial ANRS EP36 studying control HICs.Neutralizing Antibody (nAb) activities (neutralization assay, competition with broadly reactive monoclonal antibodies, and reactivity against MPER gp41 region), FcgammaR-mediated activities, antibody-dependent cell cytotoxicity (ADCC), as well autoantibody levels, were...
CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction correlates production SIV-specific immunoglobulins. However, fate their participation in SIV-induced antibody is not well understood. We investigated phenotype, function, location, molecular signature rhesus macaques. Similar to human counterparts, macaques represented a heterogeneous population respect cytokine function. In highly differentiated subpopulation...
Significantly higher levels of plasma CXCL13 [chemokine (C-X-C motif) ligand 13] were associated with the generation broadly neutralizing antibodies (bnAbs) against HIV in a large longitudinal cohort HIV-infected individuals. Germinal centers (GCs) perform remarkable task optimizing B-cell Ab responses. GCs are required for almost all receptor affinity maturation and will be critical parameter to monitor if bnAbs induced by vaccination. However, lymphoid tissue is rarely available from...
Community of antibodies against COVID-19 The severe acute respiratory syndrome coronavirus 2 spike protein is the basis many vaccines and a primary target neutralizing after infection. Coronavirus Immunotherapeutic Consortium (CoVIC), comprising 56 partners across world, has analyzed panel 269 monoclonal (mAbs) and, on competition profiles, sorted 186 mAbs that receptor binding domain into seven communities. Hastie et al . went to structurally analyze representative antibody used pseudovirus...
In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of envelope glycoprotein gp120 were an inverse correlate risk infection. To determine if V1V2-specific Abs cross-react with V1V2 from different subtypes, nature antigen used asses cross-reactivity influenced infection risk, identify immune assays for upcoming trials, new V1V2-scaffold antigens designed tested. Protein scaffold carrying subtypes A, B, C, D or CRF01_AE assayed in...
ABSTRACT Among nonneutralizing HIV-1 envelope antibodies (Abs), those capable of mediating antibody-dependent cellular cytotoxicity (ADCC) activity have been postulated to be important for control infection. ADCC-mediating Ab must recognize antigens expressed on the membrane infected cells and bind Fcγ receptor (FcR) effector cell population. However, precise targets serum ADCC antibody are poorly characterized. The human monoclonal (MAb) A32 is a isolated from an chronically person. We...
Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential mediate antiviral effector functions that could be beneficial vaccine-induced protection. Here, plasma IgG responses were assessed in three gp120 vaccine efficacy trials (RV144, Vax003, Vax004) HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 all major genetic subtypes circulating recombinant forms (CRFs) virus. In RV144, where...
Most simian-human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding CD4 (rhCD4) limits virus entry and replication could be enhanced by substituting naturally occurring simian residues at position 375, which resides a critical location in the CD4-binding pocket is under strong positive evolutionary pressure across broad spectrum of primate lentiviruses. SHIVs...
Microbiota can mislead antibodies Unlike the response to many viral infections, most people do not produce capable of clearing HIV-1. Non-neutralizing that target HIV-1's envelope glycoprotein (Env) typically dominate response, which is generated by B cells cross-react with Env and intestinal microbiota. Williams et al. analyzed samples from individuals who had received a vaccine containing protein, including gp41 subunit. Most were non-neutralizing targeted gp41. The also reacted...