Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques
Kan Luo, et al.
Kan Luo, et al.
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Research Article AIDS/HIV Vaccines

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

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.

Authors

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. Yates, Erika 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

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Figure 3

Flow cytometric detection of antigen-specific B cells.

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Flow cytometric detection of antigen-specific B cells. Peripheral blood ...
Peripheral blood mononuclear cells (PBMCs) were labeled to identify memory B cells, defined as CD3/14/16−, CD20+, and surface IgD−, and also with Env probes in 2 colors. (A) PBMCs labeled with gp120M.ConS in 2 colors are shown for the 3 rhesus macaques (RMs). (B) Cell samples from all sites obtained at necropsy were labeled with gp120M.ConS and shown as the frequency of memory B cells. Few antigen-specific B cells were observed in mesenteric lymph nodes (LNs) or terminal ileum.(C) Cell samples were also labeled with gp120AE.A244 and showed a similar pattern, except that the detected cell frequency was lower for RM 46‑11 (green triangles) in anterior pelvic LN, posterior pelvic LN, and periaortic LN. In mesenteric LN and terminal ileum, antigen-specific B cell frequencies were slightly higher for gp120AE.A244 than they were for gp120M.ConS.