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

Authors:Harari, 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
Keywords:EuroVacc 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 Date:14-Jan-2008
Publisher:Rockefeller University Press
Citation:The Journal of Experimental Medicine 205(1): 63-77 (2008)
Abstract:The 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.
Description:15 pages, 8 figures.-- PMID: 18195071 [PubMed].-- PMCID: PMC2234371.
Publisher version (URL):http://dx.doi.org/10.1084/jem.20071331
URI:http://hdl.handle.net/10261/8837
ISSN:0022-1007
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