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

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2008年 / 205卷 / 01期

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

页码：63 / 77

页数：15

共 42 条

[41] HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity [J].