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Sequential Immunization Strategies to Elicit HIV-1 bNAbs in Animal Models With a Polyclonal B Cell Repertoire

Escolano, Amelia and Gristick, Harry B. and Gautam, Rajeev and Merkenschlager, Julia and Golijanin, Jovana and Gazumyan, Anna and Pai, Joy and Bauer, Jens and Oliveira, Thiago Yukio Kikuchi and Yao, Kai-Hui and Abernathy, Morgan E. and Wang, Haoqing and Cohen, Alex and Keefe, Jennifer R. and West, Anthony P., Jr. and Martin, Malcolm A. and Bjorkman, Pamela J. and Nussenzweig, Michel (2018) Sequential Immunization Strategies to Elicit HIV-1 bNAbs in Animal Models With a Polyclonal B Cell Repertoire. AIDS Research and Human Retroviruses, 34 (S1). p. 331. ISSN 0889-2229.

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Background: Immunization regimens that can elicit broadly neutralizing antibodies (bNAbs) in humans would be an effective vaccine against HIV-1. Our previous work showed that an immunization strategy involving a sequence of Env-based germline targeting immunogens that were gradually engineered to resemble the native Env protein, successfully elicited bNAb-like antibodies in a knock-in mouse carrying the inferred germline PGT121/10-1074 antibody. Despite this achievement, immunization protocols that elicit bNAbs in systems with a polyclonal B cell repertoire have not been reported to date. The low frequencies of germline bNAb precursors in polyclonal systems hinder their activation by immunization which therefore requires high affinity immunogens. In addition, competition between different epitope-specific B cells in polyclonal germinal centers may frustrate bNAb development. Methods: Based on our previous results in knock-in mice, we have aimed to optimize sequential immunization strategies to elicit bNAbs in animal models with polyclonal B cell repertoires. Results: The results of immunization experiments in several animal models will be presented.

Item Type:Article
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URLURL TypeDescription
Wang, Haoqing0000-0003-0277-3018
Cohen, Alex0000-0001-6557-5866
Bjorkman, Pamela J.0000-0002-2277-3990
Nussenzweig, Michel0000-0003-0592-8564
Additional Information:© 2018 Mary Ann Liebert, Inc., publishers. Published Online: 22 Oct 2018.
Issue or Number:S1
Record Number:CaltechAUTHORS:20181116-085739103
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90950
Deposited By: Tony Diaz
Deposited On:16 Nov 2018 17:08
Last Modified:03 Oct 2019 20:30

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