Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes

Bancroft, Tara; DeBuysscher, Blair L.; Weidle, Connor; Schwartz, Allison; Wall, Abigail; Gray, Matthew D.; Feng, Junli; Steach, Holly R.; Fitzpatrick, Kristin S.; Gewe, Mesfin M.; Skog, Patrick D.; Doyle-Cooper, Colleen; Ota, Takayuki; Strong, Roland K.; Nemazee, David; Pancera, Marie; Stamatatos, Leonidas; McGuire, Andrew T.; Taylor, Justin J.

doi:10.1084/jem.20190164

Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes

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

DOI:https://doi.org/10.1084/jem.20190164· OSTI ID:1562601

Bancroft, Tara ^[1]; DeBuysscher, Blair L. ^[1]; Weidle, Connor ^[1]; Schwartz, Allison ^[1]; Wall, Abigail ^[1]; ^[1]; Feng, Junli ^[1]; Steach, Holly R. ^[1]; ^[1]; Gewe, Mesfin M. ^[2]; ^[3]; ^[3]; Ota, Takayuki ^[3]; Strong, Roland K. ^[1]; ^[3]; Pancera, Marie ^[1]; ^[4]; ^[4]; ^[5]

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, Department of Global Health, University of Washington, Seattle, WA
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, Department of Global Health, University of Washington, Seattle, WA, Department of Immunology, University of Washington, Seattle, WA

Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.

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

Sponsoring Organization:: James B. Pendleton Charitable Trust; National Institute of Allergy and Infectious Diseases (NIAID); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1562601

Alternate ID(s):: OSTI ID: 1625202

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

Country of Publication:: United States

Language:: English

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