Clonal Expansion and Diversification of Germinal Center and Memory B Cell Responses to Booster Immunization in Primates
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PROVIDER: PRJNA1287360 | ENA |
REPOSITORIES: ENA
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Project description:Generation of Tier 2 HIV neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses by Env immunogens remain unclear. We explored these barriers by combining a suite of innovative techniques, including longitudinal lymph node fine needle aspirates, germinal center (GC) B cell lineage tracking, and a new method for detecting and quantifying GC T follicular helper (GC Tfh) cells, in non-human primates immunized with a native-like HIV-1 Env trimer protein (BG505 SOSIP.v5.2). A majority of immunized animals (9/12) developed Tier 2 neutralizing antibodies (nAb). Tier 2 nAb development best correlated with GC B cell magnitude in response to later booster immunizations and the quality of the Tfh help. Notably, these immunological factors distinguished between qualitatively successful and unsuccessful vaccine Ab responses, as they correlated with nAb development but did not correlate with simple Env Ab binding titers. Therefore, direct probing of germinal centers in future vaccine trials is key, as this suite of technically robust approaches provides quantitation of the proximal immune correlates of neutralizing antibody development and could allow redesign of optimal multi-stage vaccination schedules.
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