Development of LIBRA-seq for the guinea pig model system as a tool for the evaluation of antibody responses to multivalent HIV-1 vaccines

Matthew J. Vukovich, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Nagarajan Raju, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Prudence Kgagudi, MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Nelia P. Manamela, MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Alexandra A. Abu-Shmais, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Kathryn R. Gripenstraw, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Perry T. Wasdin, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Xiaoying Shen, Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Bridget Dwyer, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Jumana Akoad, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Rebecca M. Lynch, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
David C. Montefiori, Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Simone I. Richardson, MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Penny L. Moore, MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Ivelin S. Georgiev, Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Document Type

Journal Article

Publication Date

12-12-2023

Journal

Journal of virology

DOI

10.1128/jvi.01478-23

Keywords

HIV-1; LIBRA-seq; guinea pig; immunogen; monoclonal antibodies; vaccine

Abstract

Multivalent vaccination with soluble Env immunogens is at the forefront of HIV-1 vaccination strategies but little is known about the influence of the number of Env strains included in vaccine cocktails. Our results suggest that adding more strains is sometimes beneficial but may be detrimental when the number of strains is too high. In addition, we adapted the LIBRA-seq platform to be compatible with guinea pig samples and isolated several tier 2 neutralizing monoclonal antibodies, some of which share V and J gene usage and >70% CDR3 identity, thus establishing the existence of public clonotypes in guinea pigs elicited through vaccination.

Department

Microbiology, Immunology, and Tropical Medicine

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