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

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.

Authors:
ORCiD logo [1];  [1];  [2];  [1];  [2];  [2];  [1];  [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2];  [3]; ORCiD logo [4];  [2]; ORCiD logo [3]; ORCiD logo [5]; ORCiD logo [3]
  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. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, University of Washington University of Washington, Department of Global Health, Seattle, WA
  4. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, University of Washington University of Washington, Department of Global Health, Seattle, WA, University of Washington University of Washington, Department of Immunology, Seattle, WA
  5. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, Howard Hughes Medical Institute, Chevy Chase, MD
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1562602
Alternate Identifier(s):
OSTI ID: 1625203
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Published Article
Journal Name:
Journal of Experimental Medicine
Additional Journal Information:
Journal Name: Journal of Experimental Medicine Journal Volume: 216 Journal Issue: 10; Journal ID: ISSN 0022-1007
Publisher:
Rockefeller University Press
Country of Publication:
United States
Language:
English
Subject:
Immunology; Research & Experimental Medicine

Citation Formats

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., and McGuire, Andrew T. Anti-idiotypic antibodies elicit anti-HIV-1–specific B cell responses. United States: N. p., 2019. Web. doi:10.1084/jem.20190446.
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. Anti-idiotypic antibodies elicit anti-HIV-1–specific B cell responses. United States. doi:10.1084/jem.20190446.
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., and McGuire, Andrew T. Thu . "Anti-idiotypic antibodies elicit anti-HIV-1–specific B cell responses". United States. doi:10.1084/jem.20190446.
@article{osti_1562602,
title = {Anti-idiotypic antibodies elicit anti-HIV-1–specific B cell responses},
author = {Dosenovic, Pia and Pettersson, Anna-Klara and Wall, Abigail and Thientosapol, Eddy S. and Feng, Junli and Weidle, Connor and Bhullar, Komal and Kara, Ervin E. and Hartweger, Harald and Pai, Joy A. and Gray, Matthew D. and Parks, K. Rachael and Taylor, Justin J. and Pancera, Marie and Stamatatos, Leonidas and Nussenzweig, Michel C. and McGuire, Andrew T.},
abstractNote = {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.},
doi = {10.1084/jem.20190446},
journal = {Journal of Experimental Medicine},
number = 10,
volume = 216,
place = {United States},
year = {2019},
month = {7}
}

Journal Article:
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DOI: 10.1084/jem.20190446

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