Multimeric Epitope-Scaffold HIV Vaccines Target V1V2 and Differentially Tune Polyfunctional Antibody Responses

Ann Hessell, Rebecca Powell, Xunqing Jiang, Christina Luo, Svenja Weiss, Vincent Dussupt, Vincenza Itri, Alisa Fox, Mariya B. Shapiro, Shilpi Pandey, Tracy Cheever, Deborah H. Fuller, Byung Park, Shelly J. Krebs, Maxim Totrov, Nancy Haigwood, Xiang Peng Kong, Susan Zolla-Pazner

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The V1V2 region of the HIV-1 envelope is the target of several broadly neutralizing antibodies (bNAbs). Antibodies to V1V2 elicited in the RV144 clinical trial correlated with a reduced risk of HIV infection, but these antibodies were without broad neutralizing activity. Antibodies targeting V1V2 also correlated with a reduced viral load in immunized macaques challenged with simian immunodeficiency virus (SIV) or simian/human immunodeficiency virus (SHIV). To focus immune responses on V1V2, we engrafted the native, glycosylated V1V2 domain onto five different multimeric scaffold proteins and conducted comparative immunogenicity studies in macaques. Vaccinated macaques developed high titers of plasma and mucosal antibodies that targeted structurally distinct V1V2 epitopes. Plasma antibodies displayed limited neutralizing activity but were functionally active for ADCC and phagocytosis, which was detectable 1–2 years after immunizations ended. This study demonstrates that multivalent, glycosylated V1V2-scaffold protein immunogens focus the antibody response on V1V2 and are differentially effective at inducing polyfunctional antibodies with characteristics associated with protection.

Original languageEnglish (US)
Pages (from-to)877-895.e6
JournalCell Reports
Volume28
Issue number4
DOIs
StatePublished - Jul 23 2019

Keywords

  • antibodies
  • binding antibody
  • co-immunization
  • Fc receptors
  • gp120 envelope glycoprotein
  • HIV envelope vaccines
  • humoral responses
  • neutralizing antibody
  • nonhuman primate
  • V1V2 domain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hessell, A., Powell, R., Jiang, X., Luo, C., Weiss, S., Dussupt, V., Itri, V., Fox, A., Shapiro, M. B., Pandey, S., Cheever, T., Fuller, D. H., Park, B., Krebs, S. J., Totrov, M., Haigwood, N., Kong, X. P., & Zolla-Pazner, S. (2019). Multimeric Epitope-Scaffold HIV Vaccines Target V1V2 and Differentially Tune Polyfunctional Antibody Responses. Cell Reports, 28(4), 877-895.e6. https://doi.org/10.1016/j.celrep.2019.06.074