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J Exp Med. 2019 Oct 7;216(10):2316-2330. doi: 10.1084/jem.20190446. Epub 2019 Jul 25.

Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.
2
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
3
University of Washington University of Washington, Department of Global Health, Seattle, WA.
4
University of Washington University of Washington, Department of Immunology, Seattle, WA.
5
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA lstamata@fredhutch.org.
6
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY nussen@mail.rockefeller.edu.
7
Howard Hughes Medical Institute, Chevy Chase, MD.
8
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA amcguire@fredhutch.org.

Abstract

Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination in diverse wild-type animals or humans, in part because B cells expressing the precursors of these antibodies do not recognize most HIV-1 envelopes (Envs). Immunogens have been designed that activate these B cell precursors in vivo, but they also activate competing off-target responses. Here we report on a complementary approach to expand specific B cells using an anti-idiotypic antibody, iv8, that selects for naive human B cells expressing immunoglobulin light chains with 5-amino acid complementarity determining region 3s, a key feature of anti-CD4 binding site (CD4bs)-specific VRC01-class antibodies. In mice, iv8 induced target cells to expand and mature in the context of a polyclonal immune system and produced serologic responses targeting the CD4bs on Env. In summary, the results demonstrate that an anti-idiotypic antibody can specifically recognize and expand rare B cells that express VRC01-class antibodies against HIV-1.

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