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

Abstract

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.

Authors:
 [1];  [1];  [1];  [1];  [1]; ORCiD logo [1];  [1];  [1]; ORCiD logo [1];  [2]; ORCiD logo [3]; ORCiD logo [3];  [3];  [1]; ORCiD logo [3];  [1]; ORCiD logo [4]; ORCiD logo [4]; ORCiD logo [5]
  1. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA
  2. Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
  3. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA
  4. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, Department of Global Health, University of Washington, Seattle, WA
  5. 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
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); James B. Pendleton Charitable Trust; National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS); National Institute of Allergy and Infectious Diseases (NIAID)
OSTI Identifier:
1562601
Alternate Identifier(s):
OSTI ID: 1625202
Grant/Contract Number:  
AC02-05CH11231; R01AI122912; R01AI081625; R21AI127249
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
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Immunology; Research & Experimental Medicine

Citation Formats

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., and Taylor, Justin J. Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes. United States: N. p., 2019. Web. doi:10.1084/jem.20190164.
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. Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes. United States. doi:10.1084/jem.20190164.
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., and Taylor, Justin J. Thu . "Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes". United States. doi:10.1084/jem.20190164.
@article{osti_1562601,
title = {Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes},
author = {Bancroft, Tara and DeBuysscher, Blair L. and Weidle, Connor and Schwartz, Allison and Wall, Abigail and Gray, Matthew D. and Feng, Junli and Steach, Holly R. and Fitzpatrick, Kristin S. and Gewe, Mesfin M. and Skog, Patrick D. and Doyle-Cooper, Colleen and Ota, Takayuki and Strong, Roland K. and Nemazee, David and Pancera, Marie and Stamatatos, Leonidas and McGuire, Andrew T. and Taylor, Justin J.},
abstractNote = {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.},
doi = {10.1084/jem.20190164},
journal = {Journal of Experimental Medicine},
number = 10,
volume = 216,
place = {United States},
year = {2019},
month = {7}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1084/jem.20190164

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