Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer.

TitleDirect Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer.
Publication TypeJournal Article
Year of Publication2016
AuthorsHavenar-Daughton C, Carnathan DG, de la Peña ATorrents, Pauthner M, Briney B, Reiss SM, Wood JS, Kaushik K, van Gils MJ, Rosales SL, van der Woude P, Locci M, Le KM, de Taeye SW, Sok D, Mohammed AUr Rasheed, Huang J, Gumber S, Garcia AP, Kasturi SP, Pulendran B, Moore JP, Ahmed R, Seumois G, Burton DR, Sanders RW, Silvestri G, Crotty S
JournalCell Rep
Volume17
Issue9
Pagination2195-2209
Date Published11/22/2016
ISSN2211-1247
Abstract

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.

DOI10.1016/j.celrep.2016.10.085
Alternate JournalCell Rep
PubMed ID27880897
PubMed Central IDPMC5142765
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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