Vaccination with Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083

Stephen R. Walsh, Zoe Moodie, Andrew J. Fiore-Gartland, Cecilia Morgan, Marissa B. Wilck, Scott M. Hammer, Susan P. Buchbinder, Spyros A. Kalams, Paul A. Goepfert, Mark J. Mulligan, Michael C. Keefer, Lindsey R. Baden, Edith M. Swann, Shannon Grant, Hasan Ahmed, Fusheng Li, Tomer Hertz, Steven G. Self, David Friedrich, Nicole FrahmHua Xin Liao, David C. Montefiori, Georgia D. Tomaras, M. Juliana Mcelrath, John Hural, Barney S. Graham, Xia Jin

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Background. Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune responses with these features are induced by prime-boost strategies, using heterologous vectors, heterologous inserts, or a combination of both. Methods. A total of 180 participants were randomly assigned to receive combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen. Results. T-cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means, 1.0; 95% confidence interval [CI],. 6-1.6; P =. 91), but heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means, 2.7; 95% CI, 1.2-5.7; P =. 01). Participants in the heterologous versus homologous insert groups had T-cell responses that targeted epitopes with greater evolutionary conservation (mean entropy [±SD], 0.32 ± 0.1 bits; P =. 003), and epitopes recognized by responders provided higher coverage (49%; P =. 035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (P =. 02,. 044, and. 045, respectively). Conclusions. These data demonstrate that vaccination with heterologous insert prime boosting increased T-cell responses to shared epitopes, while heterologous vector prime boosting increased the number of T-cell epitopes recognized.

Original languageEnglish
Pages (from-to)541-550
Number of pages10
JournalJournal of Infectious Diseases
Volume213
Issue number4
DOIs
StatePublished - 15 Feb 2016

Keywords

  • HIV-1
  • adenovirus
  • clinical trial
  • epitope mapping
  • immunogenicity
  • prime-boost
  • vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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