Leiden University Scholarly Publications

Rosario, M.; Bridgeman, A.; Quakkelaar, E.D.; Quigley, M.F.; Hill, B.J.; Knudsen, M.L.; ... ; Hanke, T. (2010)

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

Article / Letter to editor

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...Show moreA 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.Show less

HIV vaccines Macaques Prime-boost Synthetic long peptides T cells immunodeficiency-virus type-1 cervical-cancer patients healthy-volunteers siv infection viral load responses cd8(+) dna immunogenicity immunity

All authors

Rosario, M.; Bridgeman, A.; Quakkelaar, E.D.; Quigley, M.F.; Hill, B.J.; Knudsen, M.L.; Ammendola, V.; Ljungberg, K.; Borthwick, N.; E.J. im; McMichael, A.J.; Drijfhout, J.W.; Greenaway, H.Y.; Venturi, V.; Douek, D.C.; Colloca, S.; Liljestrom, P.; Nicosia, A.; Price, D.A.; Melief, C.J.M.; Hanke, T.

Date

2010-07-31

Journal

European Journal of Immunology

Volume

40

Issue

7

Pages

1973 - 1984

DOI

doi:10.1002/eji.201040344