Long peptides induce polyfunctional T cells against conserved regions of HIV-1 with superior breadth to single-gene vaccines in macaques

Maximillian Rosario, Anne Bridgeman, Esther D. Quakkelaar, Maire F. Quigley, Brenna J. Hill, Maria L. Knudsen, Virginia Ammendola, Karl Ljungberg, Nicola Borthwick, Eung Jun Im, Andrew J. McMichael, Jan W. Drijfhout, Hui Yee Greenaway, Vanessa Venturi, Daniel C. Douek, Stefano Colloca, Peter Liljeström, Alfredo Nicosia, David A. Price, Cornelis J.M. MeliefTomáš Hanke

Research output: Contribution to journalArticle

Abstract

A novel T-cell vaccine strategy designed to deal with the enormity of HIV-1 variation is described and tested for the first time in macaques to inform and complement approaching clinical trials. T-cell immunogen HIVconsv, which directs vaccine-induced responses to the most conserved regions of the HIV-1, proteome and thus both targets diverse clades in the population and reduces the chance of escape in infected individuals, was delivered using six different vaccine modalities: plasmid DNA (D), attenuated human (A) and chimpanzee (C) adenoviruses, modified vaccinia virus Ankara (M), synthetic long peptides, and Semliki Forest virus replicons. We confirmed that the initial DDDAM regimen, which mimics one of the clinical schedules (DDDCM), is highly immunogenic in macaques. Furthermore, adjuvanted synthetic long peptides divided into sub-pools and delivered into anatomically separate sites induced T-cell responses that were markedly broader than those elicited by traditional single-open-reading- frame genetic vaccines and increased by 30% the overall response magnitude compared with DDDAM. Thus, by improving both the HIV-1-derived immunogen and vector regimen/delivery, this approach could induce stronger, broader, and theoretically more protective T-cell responses than vaccines previously used in humans.

Original languageEnglish (US)
Pages (from-to)1973-1984
Number of pages12
JournalEuropean Journal of Immunology
Volume40
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • HIV vaccines
  • Macaques
  • Prime-boost
  • Synthetic long peptides
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rosario, M., Bridgeman, A., Quakkelaar, E. D., Quigley, M. F., Hill, B. J., Knudsen, M. L., Ammendola, V., Ljungberg, K., Borthwick, N., Im, E. J., McMichael, A. J., Drijfhout, J. W., Greenaway, H. Y., Venturi, V., Douek, D. C., Colloca, S., Liljeström, P., Nicosia, A., Price, D. A., ... Hanke, T. (2010). Long peptides induce polyfunctional T cells against conserved regions of HIV-1 with superior breadth to single-gene vaccines in macaques. European Journal of Immunology, 40(7), 1973-1984. https://doi.org/10.1002/eji.201040344