上海巴斯德研究所金侠研究员牵头研究发现艾滋病疫苗续...

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      上海巴斯德研究所金侠研究员牵头研究发现艾滋病疫苗续贯免疫新策略


       国际知名临床研究杂志Journal of Infectious Diseases (《传染疾病杂志》）在线发表了中国科学院上海巴斯德研究所病毒疾病及疫苗转化研究组与哈佛大学、哥伦比亚大学和罗切斯特大学等15家美国研究机构合作的研究成果“Vaccination with heterologous HIV envelope sequences and heterologous adenovirus vectors increases T cell responses to conserved regions (HVTN 083)”(不同腺病毒载体装载不同艾滋病毒E蛋白的基因重组疫苗混合免疫在人体I期临床试验中能增加保守T细胞表位的免疫反应），报道了艾滋病疫苗临床I期的研究结果。

　　目前，研发预防艾滋病毒感染的有效疫苗仍然是全球面临的巨大挑战，其主要难点是设计免疫原以覆盖病毒遗传多样性，以及如何调整免疫策略和疫苗接种方法以诱导出针对弱势抗原表位的有效T细胞免疫反应。

　　中科院上海巴斯德研究所病毒疾病及疫苗转化研究组组长金侠研究员作为该项目主席，与美国宾州大学Marissa Wilck医生和美国哈佛大学Stephen Walsh医生等合作，挑选了180名健康志愿者随机分为5组,接受不同腺病毒载体(Ad5或Ad35)表达艾滋病毒Env-A或Env-B基因的疫苗免疫。研究结果表明，不同载体或表达不同基因(Env-A或Env-B)的免疫方案能诱导出较多针对保守区域的T细胞表位，提出了增加针对共享抗原的T细胞反应的新型疫苗接种策略。

    该项目得到了美国国家卫生研究院（NIH）及其资助的艾滋病毒疫苗试验网络(HVTN)和国家推进转化科学中心等机构的共同资助。

A. 临床I期试验设计 B. T细胞表位分析方法 C. T细胞表位分析归纳 D. 载体不同作用总结

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J Infect Dis. 2015 Oct 15. pii: jiv496. [Epub ahead of print]
Vaccination with heterologous HIV envelope sequences and heterologous adenovirus vectors increases T cell responses to conserved regions (HVTN 083).
Walsh SR1, Moodie Z2, Fiore-Gartland AJ2, Morgan C2, Wilck MB3, Hammer SM4, Buchbinder SP5, Kalams SA6, Goepfert PA7, Mulligan MJ8, Keefer MC9, Baden LR3, Swann EM10, Grant S2, Ahmed H2, Li F2, Hertz T2, Self SG2, Friedrich D2, Frahm N11, Liao HX12, Montefiori DC12, Tomaras GD12, McElrath MJ13, Hural J2, Graham BS14, Jin X9; HVTN 083 Study Group, and the NIAID HIV Vaccine Trials Network.
Author information
1Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, United States Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, United States Harvard Medical School, Boston, MA, United States.
2Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
3Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, United States Harvard Medical School, Boston, MA, United States.
4Columbia University, New York, NY, United States.
5San Francisco Department of Public Health, San Francisco, CA, United States.
6Vanderbilt University School of Medicine, Nashville, TN, United States.
7University of Alabama, Birmingham, AL, United States.
8Emory University, Decatur, GA, United States.
9University of Rochester, Rochester, NY, United States.
10Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, United States.
11Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States Department of Global Health, University of Washington, Seattle, WA, United States.
12Duke Human Vaccine Institute, Duke University, Durham, NC, United States.
13Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States Department of Global Health, University of Washington, Seattle, WA, United States Departments of Medicine and Laboratory Medicine, University of Washington, Seattle, WA, United States.
14Departments of Medicine and Laboratory Medicine, University of Washington, Seattle, WA, United States.
Abstract
BACKGROUND:
 Increasing the breadth of HIV vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HVTN 083 tested whether cellular immune responses with these features are induced by prime-boost strategies employing heterologous vectors, heterologous inserts, or a combination of both.

METHODS:
 180 participants were randomized to combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen.

RESULTS:
 T cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means=1.0, 95%CI=[0.6, 1.6], p=0.91), however heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means=2.7, 95%CI=[1.2, 5.7], p=0.01). Participants in the heterologous versus homologous insert groups had T cell responses that targeted epitopes with greater evolutionary conservation (entropy 0.32±0.1 bits, p=0.003) and epitopes recognized by responders provided higher coverage (49%, p=0.035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (p=0.02, 0.044, 0.045 respectively).

CONCLUSION:
 These data demonstrate that vaccination with heterologous insert prime-boosting increased T cell responses to shared epitopes while heterologous vector prime-boosting increased the number of T cell epitopes recognized.