David M. Brown
A5064816952- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Blood groups and transfusion
- Immunodeficiency and Autoimmune Disorders
Foundation for the National Institutes of Health
2022-2025
Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01
Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise development of precision vaccines against major human pathogens. In a clinical trial the eOD-GT8 60mer germline-targeting immunogen, higher frequencies vaccine-induced VRC01-class bnAb-precursor B cells were observed in high dose compared to low group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification IGHV1-2 allele usage and...
A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01 , induced precursors of VRC01-class at high frequency majority recipients. These precursors, that target CD4 receptor binding site, had undergone...
A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by series of heterologous boosters elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States IAVI-G003 Rwanda South Africa, we evaluated safety immunogenicity mRNA-encoded nanoparticles as immunogens (both trials) first-boosting (IAVI-G002). The vaccines were generally safe well...
Abstract Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise development of precision vaccines against major human pathogens. In a clinical trial the eOD-GT8 60mer germline-targeting immunogen, higher frequencies vaccine-induced VRC01-class bnAb-precursor B cells were observed in high dose compared to low group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification IGHV1-2 allele...