Hayes Peter, Gilmour Jill, von Lieven Andrea, Gill Dilbinder, Clark Lorna, Kopycinski Jakub, Cheeseman Hannah, Chung Amy, Alter Galit, Dally Len, Zachariah Devika, Lombardo Angela, Ackland James, Sayeed Eddy, Jackson Akil, Boffito Marta, Gazzard Brian, Fast Patricia E, Cox Josephine H, Laufer Dagna
IAVI Human Immunology Laboratory, Imperial College, London, United Kingdom.
Clin Vaccine Immunol. 2013 Mar;20(3):397-408. doi: 10.1128/CVI.00637-12. Epub 2013 Jan 23.
A randomized, double-blind, placebo-controlled phase I trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of 3 doses of DNA vaccine (Advax) plus 1 dose of recombinant modified vaccinia virus Ankara (MVA) (TBC-M4) or 3 doses of TBC-M4 alone (groups A and B, respectively). Both vaccine regimens were found to be safe and well tolerated. Gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay responses were detected in 1/10 (10%) individuals in group A after three Advax primes and in 9/9 individuals (100%) after the MVA boost. In group B, IFN-γ ELISPOT responses were detected in 6/12 (50%) and 7/11 (64%) individuals after the second and third MVA vaccinations, respectively. Responses to all vaccine components, but predominantly to Env, were seen. The breadth and magnitude of the T cell response and viral inhibition were greater in group A than in group B, indicating that the quality of the T-cell response was enhanced by the DNA prime. Intracellular cytokine staining indicated that the T-cell responses were polyfunctional but were skewed toward Env with a CD4(+) phenotype. At 2 weeks after the last vaccination, HIV-specific antibody responses were detected in all (100%) group B and 1/11 (9.1%) group A vaccinees. Vaccinia virus-specific responses were detected in all (100%) group B and 2/11 (18.2%) group A vaccinees. In conclusion, HIV-specific T-cell responses were seen in the majority of volunteers in groups A and B but with a trend toward greater quality of the T-cell response in group A. Antibody responses were better in group B than in group A.
在32名未感染HIV的健康志愿者中进行了一项随机、双盲、安慰剂对照的I期试验，以评估3剂DNA疫苗（Advax）加1剂重组改良安卡拉痘苗病毒（MVA）（TBC-M4）或仅3剂TBC-M4（分别为A组和B组）的安全性和免疫原性。两种疫苗方案均被发现安全且耐受性良好。在A组中，10名个体中有1名（10%）在3剂Advax初免后通过γ干扰素（IFN-γ）酶联免疫斑点（ELISPOT）试验检测到反应，在MVA加强免疫后9名个体中有9名（100%）检测到反应。在B组中，分别在第二次和第三次MVA接种后，12名个体中有6名（50%）和11名个体中有7名（64%）检测到IFN-γ ELISPOT反应。观察到对所有疫苗成分的反应，但主要是对Env的反应。A组的T细胞反应广度和强度以及病毒抑制作用均大于B组，表明DNA初免增强了T细胞反应的质量。细胞内细胞因子染色表明，T细胞反应具有多功能性，但偏向于具有CD4(+)表型的Env。在最后一次接种后2周，所有（100%）B组和11名A组疫苗接种者中有1名（9.1%）检测到HIV特异性抗体反应。所有（100%）B组和11名A组疫苗接种者中有2名（18.2%）检测到痘苗病毒特异性反应。总之，A组和B组的大多数志愿者中都观察到了HIV特异性T细胞反应，但A组的T细胞反应质量有更高的趋势。B组的抗体反应优于A组。
