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

Publication ,  Journal Article
Walsh, SR; Moodie, Z; Fiore-Gartland, AJ; Morgan, C; Wilck, MB; Hammer, SM; Buchbinder, SP; Kalams, SA; Goepfert, PA; Mulligan, MJ; Keefer, MC ...
Published in: J Infect Dis
February 15, 2016

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. CLINICAL TRIALS REGISTRATION: NCT01095224.

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Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

February 15, 2016

Volume

213

Issue

4

Start / End Page

541 / 550

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Young Adult
  • Vaccines, Synthetic
  • Treatment Outcome
  • T-Lymphocytes
  • Middle Aged
  • Microbiology
  • Male
  • Immunization Schedule
  • Humans
 

Citation

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Walsh, S. R., Moodie, Z., Fiore-Gartland, A. J., Morgan, C., Wilck, M. B., Hammer, S. M., … HVTN 083 Study Group and the NIAID HVTN, . (2016). Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083. J Infect Dis, 213(4), 541–550. https://doi.org/10.1093/infdis/jiv496
Walsh, Stephen R., Zoe Moodie, Andrew J. Fiore-Gartland, Cecilia Morgan, Marissa B. Wilck, Scott M. Hammer, Susan P. Buchbinder, et al. “Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083.J Infect Dis 213, no. 4 (February 15, 2016): 541–50. https://doi.org/10.1093/infdis/jiv496.
Walsh SR, Moodie Z, Fiore-Gartland AJ, Morgan C, Wilck MB, Hammer SM, et al. Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083. J Infect Dis. 2016 Feb 15;213(4):541–50.
Walsh, Stephen R., et al. “Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083.J Infect Dis, vol. 213, no. 4, Feb. 2016, pp. 541–50. Pubmed, doi:10.1093/infdis/jiv496.
Walsh SR, Moodie Z, Fiore-Gartland AJ, Morgan C, Wilck MB, Hammer SM, Buchbinder SP, Kalams SA, Goepfert PA, Mulligan MJ, Keefer MC, Baden LR, Swann EM, Grant S, Ahmed H, Li F, Hertz T, Self SG, Friedrich D, Frahm N, Liao H-X, Montefiori DC, Tomaras GD, McElrath MJ, Hural J, Graham BS, Jin X, HVTN 083 Study Group and the NIAID HVTN. Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083. J Infect Dis. 2016 Feb 15;213(4):541–550.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

February 15, 2016

Volume

213

Issue

4

Start / End Page

541 / 550

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Young Adult
  • Vaccines, Synthetic
  • Treatment Outcome
  • T-Lymphocytes
  • Middle Aged
  • Microbiology
  • Male
  • Immunization Schedule
  • Humans