High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope

• Type of Material: Article
• Authors: Rohini Mopuri, Emory University; Sarah Welbourn, Emory University; Tysheena Perkins Charles, Emory University; Pooja Ralli-Jain, University of Washington; david Rosales, University of Washington; Samantha L. Burton, Emory University; Areeb Aftab, University of Washington; Kriti Karunakaran, Emory University; Kathryn Pellegrini, Emory University; William Kilembe, Center for Family Health Research in Zambia; Etienne Karita, Center for Family Health Research in Rwanda; Sandrasegaram Gnanakaran, Los Alamos National Laboratory; Amit A. Upadhyay, Emory University; Steven Bosinger, Emory University; Cynthia A. Derdeyn, University of Washington
• Language: English
• Date: 2023-10-25
• Publisher: PLOS
• Publication Version: Final Published Version
• Copyright Statement: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Universal : Public Domain Dedication
• Final Published Version (URL): https://doi.org/10.1371/journal.ppat.1011717
• Title of Journal or Parent Work: PLOS Pathogens
• Volume: 19
• Issue: 10
• Start Page: e1011717
• Grant/Funding Information: These studies were supported by the National Institutes of Health (NIH, https://www.nih.gov) grants R01 AI58706, R01 AI128837 to CAD and S10 OD026799 to SEB.
• Keywords: HIV-1 Env immunogens; HIV-1 vaccine; B cells
• Research Categories: Health Sciences, Immunology; Biology, Cell; Biology, Virology

Abstract

A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing to characterize the overall expansion, recall, and maturation of antigen specific B cells longitudinally over 90 weeks. Diversification and expansion of many B cell clonotypes occurred broadly in the absence of serum neutralization. However, in one animal that developed neutralization, two neutralizing B cell clonotypes arose from the same immunoglobulin germline and were tracked longitudinally. Early antibody variants with high identity to germline neutralized the autologous virus while later variants acquired somatic hypermutation and increased neutralization potency. The early engagement of precursors capable of neutralization with little to no SHM followed by prolonged affinity maturation allowed the two neutralizing lineages to successfully persist despite many other antigen specific B cells. The findings provide new insight into B cells responding to HIV-1 envelope during heterologous prime and boost immunization in rhesus macaques and the development of selected autologous neutralizing antibody lineages.