HIV-1 envelope glycoproteins from diverse clades differentiate antibody responses and durability among vaccinees

Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir AlamDavid C. Montefiori, Georgia D. Tomaras

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Induction of broadly cross-reactive antiviral humoral responses with the capacity to target globally diverse circulating strains is a key goal for HIV-1 immunogen design. A major gap in the field is the identification of diverse HIV-1 envelope antigens to evaluate vaccine regimens for binding antibody breadth. In this study, we define unique antigen panels to map HIV-1 vaccine-elicited antibody breadth and durability. Diverse HIV-1 envelope glycoproteins were selected based on genetic and geographic diversity to cover the global epidemic, with a focus on sexually acquired transmitted/founder viruses with a tier 2 neutralization phenotype. Unique antigenicity was determined by nonredundancy (Spearman correlation), and antigens were clustered using partitioning around medoids (PAM) to identify antigen diversity. Cross-validation demonstrated that the PAM method was better than selection by reactivity and random selection. Analysis of vaccine-elicited V1V2 binding antibody in longitudinal samples from the RV144 clinical trial revealed the striking heterogeneity among individual vaccinees in maintaining durable responses. These data support the idea that a major goal for vaccine development is to improve antibody levels, breadth, and durability at the population level. Elucidating the level and durability of vaccine-elicited binding antibody breadth needed for protection is critical for the development of a globally efficacious HIV vaccine.

Original languageEnglish
Article numbere01843-17
JournalJournal of Virology
Volume92
Issue number8
DOIs
StatePublished - 1 Apr 2018

Keywords

  • Antibody
  • Antigenicity
  • Diversity
  • Durability
  • HIV-1
  • Humoral immunity
  • Vaccine

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