Havenar-Daughton Colin, Carnathan Diane G, Torrents de la Peña Alba, Pauthner Matthias, Briney Bryan, Reiss Samantha M, Wood Jennifer S, Kaushik Kirti, van Gils Marit J, Rosales Sandy L, van der Woude Patricia, Locci Michela, Le Khoa M, de Taeye Steven W, Sok Devin, Mohammed Ata Ur Rasheed, Huang Jessica, Gumber Sanjeev, Garcia AnaPatricia, Kasturi Sudhir P, Pulendran Bali, Moore John P, Ahmed Rafi, Seumois Grégory, Burton Dennis R, Sanders Rogier W, Silvestri Guido, Crotty Shane
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA.
Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Cell Rep. 2016 Nov 22;17(9):2195-2209. doi: 10.1016/j.celrep.2016.10.085.
Generating tier 2 HIV-neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses with Env immunogens remain unclear. Here, some rhesus monkeys developed autologous tier 2 nAbs upon HIV Env trimer immunization (SOSIP.v5.2) whereas others did not. This was not because HIV Env trimers were immunologically silent because all monkeys made similar ELISA-binding antibody responses; the key difference was nAb versus non-nAb responses. We explored the immunological barriers to HIV nAb responses by combining a suite of techniques, including longitudinal lymph node fine needle aspirates. Unexpectedly, nAb development best correlated with booster immunization GC B cell magnitude and Tfh characteristics of the Env-specific CD4 T cells. Notably, these factors distinguished between successful and unsuccessful antibody responses because GC B cell frequencies and stoichiometry to GC Tfh cells correlated with nAb development, but did not correlate with total Env Ab binding titers.
Trends Mol Med. 2017-1-12
Proc Natl Acad Sci U S A. 2016-10-25
Nat Immunol. 2016-8
Annu Rev Immunol. 2016-5-20
Immunity. 2016-3-15
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