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

作者：Harari Alexandre; Bart Pierre Alexandre; Stoehr Wolfgang; Tapia Gonzalo; Garcia Miguel; Medjitna Rais Emmanuelle; Burnet Severine; Cellerai Cristina; Erlwein Otto; Barber Tristan; Moog Christiane; Liljestrom Peter; Wagner Ralf; Wolf Hans; Kraehenbuhl Jean Pierre; Esteban Mariano; Heeney Jonathan; Frachette Marie Joelle; Tartaglia James; McCormack Sheena; Babiker Abdel; Weber Jonathan; Pantaleo Giuseppe^*

来源：Journal of Experimental Medicine, 2008, 205(1): 63-77.

DOI：10.1084/jem.20071331

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 gamma 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/10(6) 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.

• 出版日期2008-1-21
• 单位河北医科大学