Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection

eLife

Kishor Mandaliya¹  Vidya Mangala Prasad²  Kelly K Lee²  Adam Dingens³  Jesse D Bloom⁴  Haidyn Weight⁵  Vrasha Chohan⁵  Laura E Doepker⁵  Mackenzie M Shipley⁵  Julie M Overbaugh⁵  Dana Arenz⁵  Frederick A Matsen⁶  Elias Harkins⁶  Duncan K Ralph⁶  Amrit Dhar⁶ 

[1] Coast Provincial General Hospital, Women’s Health Project, Mombasa, Kenya;Department of Medicinal Chemistry, University of Washington, Seattle, United States;Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States;Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States;Department of Genome Sciences, University of Washington, Seattle, United States;Howard Hughes Medical Institute, Chevy Chase, United States;Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, United States;Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States;

关键词: HIV;    broadly neutralizing antibody;    V3;    superinfection;    cryo-EM;    lineage development;    Human;   

DOI  :  10.7554/eLife.68110

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY