An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses.
An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses.
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DOI：
10.1084/jem.20071331
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发表时间：
2008-01-21
影响因子：
15.3
通讯作者：
Pantaleo, Giuseppe
中科院分区：
文献类型：
--
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
EuroVacc 02期I期试验评估了由重组DNA和痘病毒载体NYVAC组成的Prime-Boost方案的安全性和免疫原性，这两种重组DNA都表达由人类免疫缺陷病毒(HIV)1分支C分离株CN54的Env、Gag、POL和Nef多肽结构域组成的共同免疫原。40名志愿者在第0天和第4周随机接受DNA C或不接受DNA C，随后在第20周和24周接受NYVAC C。在26周和28周通过使用干扰素γ酶联免疫斑点试验定量T细胞反应来测量主要的免疫原性终点。我们的结果表明，DNA C+NYVAC C疫苗方案具有高度的免疫原性，90%的接种者检测到T细胞应答，且优于单独NYVAC C诱导的应答(33%应答者)。疫苗诱导的T细胞反应是：(A)在环境反应中(26/28周时平均480个斑点形成单位/106个单核细胞)，(B)对CD4和CD8 T细胞反应都是多功能的，(C)广泛(每个应答者平均4.2个表位)，(D)持久(在72周时70%的接种者存在T细胞反应)。疫苗诱导的T细胞反应最强，且最常针对Env(91%的疫苗)，但48%的接种者对Gag-Pol-Nef的反应较小。这些结果支持了痘病毒平台在HIV疫苗领域的发展和DNA C+NYVAC C疫苗方案的进一步临床开发。
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 γ 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.
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影响因子：
4.4
作者：
Harari, A;Vallelian, F;Pantaleo, G
通讯作者：
Pantaleo, G
影响因子：
20.3
作者：
Harari, A;Petitpierre, S;Pantaleo, G
通讯作者：
Pantaleo, G
影响因子：
4.1
作者：
Bart, Pierre-Alexandre;Harari, Alexandre;Pantaleo, Giuseppe
通讯作者：
Pantaleo, Giuseppe
影响因子：
5.5
作者：
Elena Gomez, Carmen;Luis Najera, Jose;Esteban, Mariano
通讯作者：
Esteban, Mariano
影响因子：
64.8
作者：
Champagne, P;Ogg, GS;Pantaleo, G
通讯作者：
Pantaleo, G