The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization
Lin Lei,
Yuhe R. Yang,
Karen Tran,
Yimeng Wang,
Chi-I Chiang,
Gabriel Ozorowski,
Yongli Xiao,
Andrew B. Ward,
Richard T. Wyatt,
Yuxing Li
Affiliations
Lin Lei
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA
Yuhe R. Yang
Department of Integrative Structural and Computation Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Karen Tran
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
Yimeng Wang
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA
Chi-I Chiang
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA
Gabriel Ozorowski
Department of Integrative Structural and Computation Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Yongli Xiao
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
Andrew B. Ward
Department of Integrative Structural and Computation Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Richard T. Wyatt
IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
Yuxing Li
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Center of Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding author
Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target.
