Journal
CELL REPORTS
Volume 17, Issue 9, Pages 2195-2209Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.10.085
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Funding
- Scripps CHAVI-ID (NIH Grant) [UM1-AI100663]
- National Primate Research Center [P51 RR000165/OD011132]
- NIAID (Emory Center for AIDS Research, NIH) [P30-AI-504]
- Gates Foundation
- European Research Council [ERC-StG-2011-280829-SHEV]
- NIAID (HIVRAD, NIH Grant) [P01 AI110657]
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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 un-successful 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.
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