Division of Infectious Disease, Department of Internal Medicine, University of California at Davis, Sacramento, CA 95618, USA.
J Infect Dis. 2010 Jan 1;201(1):132-41. doi: 10.1086/648591.
We report composite results from the Merck phase I program of near-consensus clade B human immunodeficiency virus (HIV) type 1 gag vaccines.
Healthy HIV-uninfected adults were enrolled in 6 blinded placebo-controlled studies evaluating the immunogenicity of (1) a 4-dose regimen of a DNA vaccine, (2) a 3-dose priming regimen of the DNA vaccine with a booster dose of an adenovirus type 5 (Ad5)-vectored vaccine, or (3) a 3-dose regimen of the Ad5 vaccine. The DNA plasmid was provided with or without an aluminum phosphate or CRL1005 adjuvant. The primary end point was the unfractionated HIV-1 gag-specific interferon gamma enzyme-linked immunospot (ELISpot) response 4 weeks after the final dose.
Overall, 254 (83%) of 307 subjects randomized to the vaccine groups were evaluable. Adjuvants did not enhance immunogenicity of the DNA vaccine. Postboost ELISpot responder frequencies were higher for Ad5-containing regimens than for the DNA/DNA regimen (33%) but were similar for DNA/Ad5 (55%) and Ad5/Ad5 (50%). DNA/DNA elicited mainly a CD4 response, whereas Ad5/Ad5 elicited mainly a CD8 response; DNA/Ad5 generated CD4 and CD8 responses comparable to those of DNA/DNA and Ad5/Ad5, respectively.
The DNA vaccine alone or as a priming regimen for the Ad5 vaccine did not increase unfractionated ELISpot responses compared with the Ad5 vaccine alone. Qualitative T cell responses to different vaccine regimens deserve further study.
我们报告了默克公司 B 型人类免疫缺陷病毒（HIV）1 型 gag 疫苗 I 期方案的综合结果。
健康的 HIV 未感染者被纳入 6 项盲法安慰剂对照研究，评估了（1）4 剂 DNA 疫苗方案，（2）DNA 疫苗 3 剂初免加腺病毒 5 型（Ad5）疫苗加强针，或（3）Ad5 疫苗 3 剂方案的免疫原性。DNA 质粒与磷酸铝或 CRL1005 佐剂联合使用或不联合使用。主要终点是最后一剂后 4 周时 HIV-1 gag 特异性干扰素 γ 酶联免疫斑点（ELISpot）反应的未分级总和。
总共 307 名随机分配到疫苗组的受试者中，254 名（83%）可评估。佐剂并未增强 DNA 疫苗的免疫原性。含 Ad5 方案的加强后 ELISpot 应答者频率高于 DNA/DNA 方案（33%），但与 DNA/Ad5（55%）和 Ad5/Ad5（50%）方案相似。DNA/DNA 主要诱导 CD4 反应，而 Ad5/Ad5 主要诱导 CD8 反应；DNA/Ad5 产生的 CD4 和 CD8 反应分别与 DNA/DNA 和 Ad5/Ad5 相当。
与单独使用 Ad5 疫苗相比，单独使用 DNA 疫苗或作为 Ad5 疫苗的初免方案并未增加未分级 ELISpot 反应。不同疫苗方案的定性 T 细胞反应值得进一步研究。
