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表达HIV-1病毒样颗粒的DNA和重组改良安卡拉痘苗病毒疫苗的1期安全性和免疫原性测试。

Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles.

作者信息

Goepfert Paul A, Elizaga Marnie L, Sato Alicia, Qin Li, Cardinali Massimo, Hay Christine M, Hural John, DeRosa Stephen C, DeFawe Olivier D, Tomaras Georgia D, Montefiori David C, Xu Yongxian, Lai Lilin, Kalams Spyros A, Baden Lindsey R, Frey Sharon E, Blattner William A, Wyatt Linda S, Moss Bernard, Robinson Harriet L

机构信息

Department of Medicine, University of Alabama at Birmingham, AL 35294, USA.

出版信息

J Infect Dis. 2011 Mar 1;203(5):610-9. doi: 10.1093/infdis/jiq105. Epub 2011 Jan 31.

DOI:10.1093/infdis/jiq105
PMID:21282192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3072720/
Abstract

BACKGROUND

Recombinant DNA and modified vaccinia virus Ankara (rMVA) vaccines represent a promising approach to an HIV/AIDS vaccine. This Phase 1 clinical trial compared the safety and immunogenicity of a rMVA vaccine administered with and without DNA vaccine priming

METHODS

GeoVax pGA2/JS7 DNA (D) and MVA/HIV62 (M) vaccines encode noninfectious virus-like particles. Intramuscular needle injections were used to deliver placebo, 2 doses of DNA followed by 2 doses of rMVA (DDMM), one dose of DNA followed by 2 doses of rMVA (DMM), or 3 doses of rMVA (MMM) to HIV-seronegative participants.

RESULTS

Local and systemic symptoms were mild or moderate. Immune response rates for CD4 + and CD8 + T cells were highest in the DDMM group and lowest in the MMM group (77% vs 43% CD4 + and 42% vs 17% CD8 +). In contrast, response rates for Env binding and neutralizing Ab were highest in the MMM group. The DMM group had intermediate response rates. A 1/10th-dose DDMM regimen induced similar T cell but reduced Ab response rates compared with the full-dose DDMM.

CONCLUSIONS

MVA62 was well tolerated and elicited different patterns of T cell and Ab responses when administered alone or in combination with the JS7 DNA vaccine.

摘要

背景

重组DNA疫苗和改良安卡拉痘苗病毒(rMVA)疫苗是一种很有前景的HIV/AIDS疫苗研发方法。这项1期临床试验比较了接种和未接种DNA疫苗预免疫情况下rMVA疫苗的安全性和免疫原性。

方法

GeoVax pGA2/JS7 DNA(D)疫苗和MVA/HIV62(M)疫苗编码无感染性的病毒样颗粒。通过肌肉注射将安慰剂、2剂DNA疫苗后接2剂rMVA疫苗(DDMM)、1剂DNA疫苗后接2剂rMVA疫苗(DMM)或3剂rMVA疫苗(MMM)给予HIV血清阴性的受试者。

结果

局部和全身症状为轻至中度。DDMM组CD4+和CD8+T细胞的免疫应答率最高,MMM组最低(CD4+分别为77%对43%,CD8+分别为42%对17%)。相反,Env结合抗体和中和抗体的应答率在MMM组最高。DMM组的应答率处于中间水平。与全剂量DDMM方案相比,1/10剂量的DDMM方案诱导的T细胞应答相似,但抗体应答率降低。

结论

MVA62耐受性良好,单独使用或与JS7 DNA疫苗联合使用时可引发不同模式的T细胞和抗体应答。

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