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

Dosenovic, Pia; Pettersson, Anna-Klara; Wall, Abigail; Thientosapol, Eddy S.; Feng, Junli; Weidle, Connor; Bhullar, Komal; Kara, Ervin E.; Hartweger, Harald; Pai, Joy A.; Gray, Matthew D.; Parks, K. Rachael; Taylor, Justin J.; Pancera, Marie; Stamatatos, Leonidas; Nussenzweig, Michel C.; McGuire, Andrew T.

doi:10.1084/jem.20190446

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

Journal Article · Thu Jul 25 00:00:00 EDT 2019 · Journal of Experimental Medicine

DOI:https://doi.org/10.1084/jem.20190446· OSTI ID:1562602

; Pettersson, Anna-Klara; Wall, Abigail; Thientosapol, Eddy S.; Feng, Junli; Weidle, Connor; Bhullar, Komal; Kara, Ervin E.; ; ; ; Parks, K. Rachael; ; Pancera, Marie; ; ;

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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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1562602

Alternate ID(s):: OSTI ID: 1625203

Journal Information:: Journal of Experimental Medicine, Journal Name: Journal of Experimental Medicine Journal Issue: 10 Vol. 216; ISSN 0022-1007

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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