Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection
Year: 2021
Type: article
Abstract: Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. BnAb QA013.2 bound initial and superinfecting viral Env, despite its probable naive progenitor only recognizing the superinfecting strain, suggesting both viruses influenced this lineage. A 4.15 Å cryo-EM structure of QA013.2 bound to native-like trimer showed recognition of V3 signatures (N301/N332 and GDIR). QA013.2 relies less on CDRH3 and more on framework and CDRH1 for affinity and breadth compared to other V3/glycan-specific bnAbs. Antigenic profiling revealed that viral escape was achieved by changes in the structurally-defined epitope and by mutations in V1. These results highlight shared and novel properties of QA013.2 relative to other V3/glycan-specific bnAbs in the setting of sequential, diverse antigens.
Source: eLife
DOI: 10.7554/elife.68110
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Structural and dynamic traits underlying phenotypic variation in HIV-1 Env, Complete mapping of immune selection from antibodies to HIV, Characterizing the broad antibody response to HIV superinfection, Blending deep learning with probabilistic mechanistic models to predict and understand the evolution and function of adaptive immune receptors, Dynamics and Evolution of Immune Responses to Influenza Viruses, G9000142776, Immune Responses to Malaria, HIV and SARS-CoV-2 Infection and Immunization
OpenAlex ID: W3180145624