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An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses

AuthorsHarari, Alexandre; Bart, Pierre-Alexandre; Stöhr, Wolfgang; Tapia, Gonzalo; García Cabezas, Miguel Ángel; Medjitna-Rais, Emmanuelle; Burnet, Séverine; Cellerai, Cristina; Erlwein, Otto; Barber, Tristan; Moog, Christiane; Liljeström, Peter; Wagner, Ralf; Wolf, Hans; Kraehenbuhl, Jean-Pierre; Esteban, Mariano ; Heeney, Jonathan L.; Frachette, Marie-Joelle; Tartaglia, James; McCormack, Sheena; Babiker, Abdel; Weber, Jonathan; Pantaleo, Giuseppe
KeywordsEuroVacc 02 clinical trial
New York vaccinia virus (NYVAC)
Human immunodeficiency virus (HIV)-1
T-cell immune response
DNA C plus NYVAC C vaccine
HIV vaccines
Issue Date14-Jan-2008
PublisherRockefeller University Press
CitationThe Journal of Experimental Medicine 205(1): 63-77 (2008)
AbstractThe EuroVacc 02 phase I trial has evaluated the safety and immunogenicity of a prime-boost regimen comprising recombinant DNA and the poxvirus vector NYVAC, both expressing a common immunogen consisting of Env, Gag, Pol, and Nef polypeptide domain from human immunodeficiency virus (HIV)-1 clade C isolate, CN54. 40 volunteers were randomized to receive DNA C or nothing on day 0 and at week 4, followed by NYVAC C at weeks 20 and 24. The primary immunogenicity endpoints were measured at weeks 26 and 28 by the quantification of T cell responses using the interferon enzyme-linked immunospot assay. Our results indicate that the DNA C plus NYVAC C vaccine regimen was highly immunogenic, as indicated by the detection of T cell responses in 90% of vaccinees and was superior to responses induced by NYVAC C alone (33% of responders). The vaccine-induced T cell responses were (a) vigorous in the case of the env response (mean 480 spot-forming units/106 mononuclear cells at weeks 26/28), (b) polyfunctional for both CD4 and CD8 T cell responses, (c) broad (the average number of epitopes was 4.2 per responder), and (d) durable (T cell responses were present in 70% of vaccinees at week 72). The vaccine-induced T cell responses were strongest and most frequently directed against Env (91% of vaccines), but smaller responses against Gag-Pol-Nef were also observed in 48% of vaccinees. These results support the development of the poxvirus platform in the HIV vaccine field and the further clinical development of the DNA C plus NYVAC C vaccine regimen.
Description15 pages, 8 figures.-- PMID: 18195071 [PubMed].-- PMCID: PMC2234371.
Publisher version (URL)http://dx.doi.org/10.1084/jem.20071331
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