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];
[3];
[3];
[3];
[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
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- 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 and experimental medicine; infectious disease; host defense
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. https://doi.org/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. https://doi.org/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}
}
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Figure 1: Identification and characterization of anti-iglb12 idiotypes. (A) BLI analysis of the purified products of four hybridomas named IB1, IB2, IB3, and IB5 binding to different concentrations of iglb12. (B) The affinity (KD) of the anti-idiotype for iglb12 was calculated based upon the on rate (KON) and off ratemore »
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Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.