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Mixed Origins: HIV gp120-specific memory develops from pre-existing memory and naïve B cells following vaccination in humans

Madhubanti Basu, Michael S. Piepenbrink, Christopher Fucile, Catherine A. Bunce, Li-Xing Man, Jane Liesveld, Alexander F. Rosenberg, Michael C. Keefer, James J. Kobie
doi: https://doi.org/10.1101/2021.09.01.458551
Madhubanti Basu
1Infectious Diseases Division, University of Alabama at Birmingham, Birmingham, AL USA
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Michael S. Piepenbrink
1Infectious Diseases Division, University of Alabama at Birmingham, Birmingham, AL USA
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Christopher Fucile
2Informatics Institute, University of Alabama at Birmingham, Birmingham, AL USA
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Catherine A. Bunce
3Infectious Diseases Division, University of Rochester, Rochester, NY USA
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Li-Xing Man
4Department of Otolaryngology Head and Neck Surgery, University of Rochester, Rochester, NY USA
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Jane Liesveld
5Division of Hematology/Oncology, University of Rochester, Rochester, NY USA
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Alexander F. Rosenberg
2Informatics Institute, University of Alabama at Birmingham, Birmingham, AL USA
6Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL USA
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Michael C. Keefer
3Infectious Diseases Division, University of Rochester, Rochester, NY USA
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James J. Kobie
1Infectious Diseases Division, University of Alabama at Birmingham, Birmingham, AL USA
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  • For correspondence: jjkobie@uabmc.edu
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Abstract

The most potent and broad HIV envelope (Env)-specific antibodies often when reverted to their inferred germline versions representing the naïve B cell receptor, fail to bind Env suggesting that the initial responding B cell population is not exclusively comprised of a naïve population, but also a pre-existing cross-reactive antigen-experienced B cell pool that expands following Env exposure. Previously we isolated gp120-reactive monoclonal antibodies (mAbs) from participants in HVTN 105, an HIV vaccine trial. Using deep sequencing VH-lineage tracking we identified several of these mAb lineages in pre-immune peripheral blood. Several of these pre-immune lineages also persisted in the bone marrow, including CD138+ long-lived plasma cell compartment, ∼7 months after the final vaccination. The majority of the pre-immune lineage members included IgM, however IgG and IgA members were also prevalent and exhibited somatic hypermutation. These results suggest that vaccine-induced gp120-specific antibody lineages originate from both naïve and cross-reactive memory B cells.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 01, 2021.
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Mixed Origins: HIV gp120-specific memory develops from pre-existing memory and naïve B cells following vaccination in humans
Madhubanti Basu, Michael S. Piepenbrink, Christopher Fucile, Catherine A. Bunce, Li-Xing Man, Jane Liesveld, Alexander F. Rosenberg, Michael C. Keefer, James J. Kobie
bioRxiv 2021.09.01.458551; doi: https://doi.org/10.1101/2021.09.01.458551
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Mixed Origins: HIV gp120-specific memory develops from pre-existing memory and naïve B cells following vaccination in humans
Madhubanti Basu, Michael S. Piepenbrink, Christopher Fucile, Catherine A. Bunce, Li-Xing Man, Jane Liesveld, Alexander F. Rosenberg, Michael C. Keefer, James J. Kobie
bioRxiv 2021.09.01.458551; doi: https://doi.org/10.1101/2021.09.01.458551

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