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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Luo, K; Liao, H-X; 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, S-M; 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; Moody, MA

Published Date

  • December 8, 2016

Published In

Volume / Issue

  • 1 / 20

Start / End Page

  • e88522 -

PubMed ID

  • 27942585

Pubmed Central ID

  • PMC5135278

International Standard Serial Number (ISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.88522

Language

  • eng

Conference Location

  • United States