National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI144462
United States
Bill & Melinda Gates Foundation
OPP1196345/INV-008813
United States
Citation
Journal: Cell Rep / Year: 2020 Title: Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques. Authors: Fangzhu Zhao / Collin Joyce / Alison Burns / Bartek Nogal / Christopher A Cottrell / Alejandra Ramos / Trevor Biddle / Matthias Pauthner / Rebecca Nedellec / Huma Qureshi / Rosemarie Mason / ...Authors: Fangzhu Zhao / Collin Joyce / Alison Burns / Bartek Nogal / Christopher A Cottrell / Alejandra Ramos / Trevor Biddle / Matthias Pauthner / Rebecca Nedellec / Huma Qureshi / Rosemarie Mason / Elise Landais / Bryan Briney / Andrew B Ward / Dennis R Burton / Devin Sok / Abstract: BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs) ...BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs). Rhesus macaques are considered the most appropriate pre-clinical animal model for monitoring antibody (Ab) responses. Accordingly, we report here the isolation of 45 BG505 autologous neutralizing antibodies (nAbs) with multiple specificities from SOSIP-immunized and BG505 SHIV-infected rhesus macaques. We associate the most potent neutralization with two epitopes: the C3/V5 and V1/V3 regions. We show that all of the nAbs bind in close proximity to known bnAb epitopes and might therefore sterically hinder elicitation of bnAbs. We also identify a "public clonotype" that targets the immunodominant C3/V5 nAb epitope, which suggests that common antibody rearrangements might help determine humoral responses to Env immunogens. The results highlight important considerations for vaccine design in anticipation of results of the BG505 SOSIP trimer in clinical trials.
History
Deposition
Jul 31, 2020
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Header (metadata) release
Sep 23, 2020
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Map release
Sep 23, 2020
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Update
Sep 23, 2020
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Current status
Sep 23, 2020
Processing site: RCSB / Status: Released
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