Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env TrimerReportar como inadecuado




Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal Title:

Cell Reports

Volume:

Volume 17, Number 9

Publisher:

publisher | 2016-11-22, Pages 2195-2209

Type of Work:

Article | Final Publisher PDF

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.

Subjects: Health Sciences, Immunology - Health Sciences, General - Research Funding: This work was supported by the Scripps CHAVI-ID SC, GS, DB, BP, RA and National Primate Research Center funding P51 RR000165-OD011132 to the Yerkes National Primate Research Center, with additional grants from NIAID Emory Center for AIDS Research, NIH Grant # P30-AI-504, GS. HIVRAD, RWS, JPM, the Gates Foundation CAVD BP, SC, and the European Research Council ERC-StG-2011–280829-SHEV, RWS.

Keywords: vaccines -



Autor: Colin Havenar-Daughton, Diane G. Carnathan, Alba Torrents de la Peña, Matthias Pauthner, Bryan Briney, Samantha M. Reiss, Jennif

Fuente: https://open.library.emory.edu/



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