1. Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques.
- Author
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Luo K, Liao HX, Zhang R, Easterhoff D, Wiehe K, Gurley TC, Armand LC, Allen AA, Von Holle TA, Marshall DJ, Whitesides JF, Pritchett J, Foulger A, Hernandez G, Parks R, Lloyd KE, Stolarchuk C, Sawant S, Peel J, Yates NL, Dunford E, Arora S, Wang A, Bowman CM, Sutherland LL, Scearce RM, Xia SM, Bonsignori M, Pollara J, Edwards RW, Santra S, Letvin NL, Tartaglia J, Francis D, Sinangil F, Lee C, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Michael NL, Kim JH, Alam SM, Vandergrift NA, Ferrari G, Montefiori DC, Tomaras GD, Haynes BF, and Moody MA
- Subjects
- Animals, HIV Antibodies analysis, HIV Envelope Protein gp120 administration & dosage, Immunization, Secondary, Immunoglobulin G analysis, Macaca mulatta, AIDS Vaccines immunology, B-Lymphocytes classification, HIV Envelope Protein gp120 immunology, HIV Infections prevention & control, Immunity, Mucosal
- 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., Competing Interests: J. Tartaglia was an employee of Sanofi and D. Francis, F. Sinangil, and C. Lee were employees of Global Solutions for Infectious Diseases at the time this study was performed. D. Francis, F. Sinangil, and C. Lee are former employees of VaxGen.
- Published
- 2016
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