Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses.
Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses.
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DOI：
10.1371/journal.pone.0009015
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发表时间：
2010-02-02
期刊：
影响因子：
3.7
通讯作者：
VRC 010 Study Team
中科院分区：
文献类型：
--
作者：
Koup RA;Roederer M;Lamoreaux L;Fischer J;Novik L;Nason MC;Larkin BD;Enama ME;Ledgerwood JE;Bailer RT;Mascola JR;Nabel GJ;Graham BS;VRC 009 Study Team;VRC 010 Study Team
诱导与不同亚型相关的HIV-1特异性T细胞反应是HIV疫苗开发的一个主要目标。在临床前研究中，使用异源基因疫苗载体的Prime-Boost方案已经诱导了强大的多功能T细胞反应。第一次评估DNA预置和重组腺病毒血清5型(RAd5)增强免疫原性的机会是在参加过HIV-1特异性DNA疫苗研究的受试者中进行开放标记翻转试验。所有受试者在rAd5增强前后都进行了分离，以深入研究异源DNA/rAd5 Prime-Boost组合诱导的T细胞和抗体反应。RAd5增强治疗耐受性良好，无严重不良反应。与单独接种DNA或rAd5疫苗相比，顺序注射DNA/rAd5诱导的HIV-1特异性CD8+T细胞应答增加了7倍，抗体滴度增加了100倍。对初代分离株无明显中和抗体活性。疫苗激发的CD4+和CD8+T细胞表达多种功能，主要是长期(CD127+)中枢或效应记忆T细胞，并在血液中持续6个月。在Gag和Env中定位的表位显示了部分交叉识别。以载体为基础的疫苗抗原基因递送的异种初始增强免疫策略是一种有效的诱导抗体和T细胞反应的免疫策略。ClinicalTrails.gov NCT00102089，NCT00108654
Induction of HIV-1-specific T-cell responses relevant to diverse subtypes is a major goal of HIV vaccine development. Prime-boost regimens using heterologous gene-based vaccine vectors have induced potent, polyfunctional T cell responses in preclinical studies. The first opportunity to evaluate the immunogenicity of DNA priming followed by recombinant adenovirus serotype 5 (rAd5) boosting was as open-label rollover trials in subjects who had been enrolled in prior studies of HIV-1 specific DNA vaccines. All subjects underwent apheresis before and after rAd5 boosting to characterize in depth the T cell and antibody response induced by the heterologous DNA/rAd5 prime-boost combination. rAd5 boosting was well-tolerated with no serious adverse events. Compared to DNA or rAd5 vaccine alone, sequential DNA/rAd5 administration induced 7-fold higher magnitude Env-biased HIV-1-specific CD8+ T-cell responses and 100-fold greater antibody titers measured by ELISA. There was no significant neutralizing antibody activity against primary isolates. Vaccine-elicited CD4+ and CD8+ T-cells expressed multiple functions and were predominantly long-term (CD127+) central or effector memory T cells and that persisted in blood for >6 months. Epitopes mapped in Gag and Env demonstrated partial cross-clade recognition. Heterologous prime-boost using vector-based gene delivery of vaccine antigens is a potent immunization strategy for inducing both antibody and T-cell responses. ClinicalTrails.gov NCT00102089, NCT00108654
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影响因子：
5.4
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