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Published on: December 23, 2016
Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques
Fangzhu Zhao1, Collin Joyce1, Alison Burns1
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Researchers isolated 45 neutralizing antibodies (nAbs) from macaques immunized with BG505 SOSIP, a promising HIV vaccine candidate. These antibodies target key regions and may impact the development of broadly neutralizing antibodies (bnAbs).
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- BG505 SOSIP is a near-native recombinant HIV Envelope (Env) trimer with potential for sequential immunogen regimens.
- Inducing broadly neutralizing antibodies (bnAbs) is a key goal for effective HIV vaccines.
- Rhesus macaques serve as a critical pre-clinical model for evaluating antibody responses.
Purpose of the Study:
- To isolate and characterize autologous neutralizing antibodies (nAbs) from rhesus macaques immunized with BG505 SOSIP or infected with BG505 SHIV.
- To identify the specific epitopes targeted by these nAbs and assess their potential impact on bnAb elicitation.
- To investigate the role of public clonotypes in shaping humoral responses to HIV Env immunogens.
Main Methods:
- Isolation and characterization of 45 BG505 autologous neutralizing antibodies (nAbs).
- Epitope mapping to identify targeted regions, specifically C3/V5 and V1/V3.
- Analysis of antibody binding proximity to known bnAb epitopes and identification of public clonotypes.
Main Results:
- Isolation of 45 nAbs with diverse specificities from immunized and infected macaques.
- Potent neutralization associated with C3/V5 and V1/V3 epitopes.
- Identified nAbs bind near known bnAb epitopes, potentially causing steric hindrance.
- Discovered a public clonotype targeting the immunodominant C3/V5 epitope.
Conclusions:
- Autologous nAbs elicited by BG505 SOSIP can target key epitopes and may influence the development of bnAbs.
- The identification of a public clonotype suggests common antibody rearrangements contribute to humoral responses.
- Findings provide crucial insights for optimizing future HIV vaccine designs based on BG505 SOSIP trimer immunogens.
