Vaccine Research Center, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS One. 2010 Feb 2;5(2):e9015. doi: 10.1371/journal.pone.0009015.
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.
ClinicalTrials.gov NCT00102089, NCT00108654.
诱导与不同亚型相关的 HIV-1 特异性 T 细胞反应是 HIV 疫苗开发的主要目标。使用异源基因疫苗载体的初免-加强方案已在临床前研究中诱导出有效的、多功能的 T 细胞反应。
首次有机会评估 DNA 初免后用重组腺病毒血清型 5（rAd5）加强的免疫原性，是在先前 HIV-1 特异性 DNA 疫苗研究中入组的受试者中进行的开放性标签滚转试验。所有受试者在 rAd5 加强后进行外周血白细胞分离术，以深入描述异源 DNA/rAd5 初免-加强组合诱导的 T 细胞和抗体反应。
rAd5 加强的耐受性良好，无严重不良事件。与 DNA 或 rAd5 疫苗单独使用相比，序贯 DNA/rAd5 给药诱导出 7 倍以上的 Env 偏向性 HIV-1 特异性 CD8+T 细胞反应和 100 倍以上的 ELISA 测量的抗体滴度。对原发性分离物没有显著的中和抗体活性。疫苗诱导的 CD4+和 CD8+T 细胞表达多种功能，主要是长期（CD127+）中央或效应记忆 T 细胞，在血液中持续存在>6 个月。在 Gag 和 Env 中映射的表位显示出部分跨群识别。
使用基于载体的基因传递疫苗抗原的异源初免-加强是一种有效的免疫策略，可诱导抗体和 T 细胞反应。
ClinicalTrials.gov NCT00102089，NCT00108654。
