Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques

Kan Luo, Hua Xin Liao, Ruijun Zhang, David Easterhoff, Kevin Wiehe, Thaddeus C. Gurley, Lawrence C. Armand, Ashley A. Allen, Tarra A. von Holle, Dawn J. Marshall, John F. Whitesides, Jamie Pritchett, Andrew Foulger, Giovanna Hernandez, Robert Parks, Krissey E. Lloyd, Christina Stolarchuk, Sheetal Sawant, Jessica Peel, Nicole L. YatesErika Dunford, Sabrina Arora, Amy Wang, Cindy M. Bowman, Laura L. Sutherland, Richard M. Scearce, Shi Mao Xia, Mattia Bonsignori, Justin Pollara, R. Whitney Edwards, Sampa Santra, Norman L. Letvin, James Tartaglia, Donald Francis, Faruk Sinangil, Carter Lee, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Nelson L. Michael, Jerome H. Kim, S. Munir Alam, Nathan A. Vandergrift, Guido Ferrari, David C. Montefiori, Georgia D. Tomaras, Barton F. Haynes, M. Anthony Moody*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The ALVAC prime/ALVAC + AIDSVAX B/E boost RV144 vaccine trial induced an estimated 31% efficacy in a low-risk cohort where HIV-1 exposures were likely at mucosal surfaces. An immune correlates study demonstrated that antibodies targeting the V2 region and in a secondary analysis antibody-dependent cellular cytotoxicity (ADCC), in the presence of low envelope-specific (Env-specific) IgA, correlated with decreased risk of infection. Thus, understanding the B cell repertoires induced by this vaccine in systemic and mucosal compartments are key to understanding the potential protective mechanisms of this vaccine regimen. We immunized rhesus macaques with the ALVAC/AIDSVAX B/E gp120 vaccine regimen given in RV144, and then gave a boost 6 months later, after which the animals were necropsied. We isolated systemic and intestinal vaccine Env-specific memory B cells. Whereas Env-specific B cell clonal lineages were shared between spleen, draining inguinal, anterior pelvic, posterior pelvic, and periaortic lymph nodes, members of Env-specific B cell clonal lineages were absent in the terminal ileum. Env-specific antibodies were detectable in rectal fluids, suggesting that IgG antibodies present at mucosal sites were likely systemically produced and transported to intestinal mucosal sites.

Original languageEnglish
Article numbere88522
JournalJournal of Clinical Investigation
Volume1
Issue number20
DOIs
StatePublished - 8 Dec 2016
Externally publishedYes

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