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

被引:247
作者
Harari, Alexandre [1 ]
Bart, Pierre-Alexandre [1 ]
Stoehr, Wolfgang [2 ]
Tapia, Gonzalo [1 ]
Garcia, Miguel [1 ]
Medjitna-Rais, Emmanuelle [1 ]
Burnet, Severine [1 ]
Cellerai, Cristina [1 ]
Erlwein, Otto [3 ]
Barber, Tristan [3 ]
Moog, Christiane [4 ]
Liljestrom, Peter [5 ]
Wagner, Ralf [6 ]
Wolf, Hans [6 ]
Kraehenbuhl, Jean-Pierre [1 ]
Esteban, Mariano [7 ]
Heeney, Jonathan [8 ,9 ]
Frachette, Marie-Joelle [10 ]
Tartaglia, James [11 ]
McCormack, Sheena [2 ]
Babiker, Abdel [2 ]
Weber, Jonathan [3 ]
Pantaleo, Giuseppe [1 ]
机构
[1] Univ Lausanne, Ctr Hosp Univ Vaudois, Dept Med, Div Immunol & Allergy, CH-1011 Lausanne, Switzerland
[2] MRC Clin Trials Unit, London NW1 2DA, England
[3] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, London SW7 2AZ, England
[4] Univ Strasbourg, Inst Virol, F-67070 Strasbourg, France
[5] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden
[6] Univ Regensburg, Inst Med Microbiol, D-93053 Regensburg, Germany
[7] CSIC, Ctr Nacl Biotecnol, Dept Mol & Cellular Biol, Madrid 28049, Spain
[8] BPRC, Dept Virol, NL-2280 GH Rijswijk, Netherlands
[9] Univ Cambridge, Cambridge CB2 1TN, England
[10] Sanofi Pasteur, F-69367 Lyon, France
[11] Sanofi Pasteur, Toronto, ON M2R 3T4, Canada
基金
英国医学研究理事会;
关键词
D O I
10.1084/jem.20071331
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:63 / 77
页数:15
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