N Engl J Med:南方医科大学张其威教授发表埃博拉疫苗研究通...

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近日，《新英格兰医学杂志》发表了我校公共卫生与热带医学学院张其威关于《Chimpanzee AdenovirusVector Ebola Vaccine--Preliminary Report》的通讯论文，这是该杂志埃博拉疫苗研究方面发表的第一篇来自中国的报道，张其威为第一作者和通讯作者，主要研究方向为腺病毒疫苗载体和进化。

埃博拉出血热是一种严重的出血性疾病，由毒力极强的埃博拉病毒(EBOV)感染引起。致死率高达90%，目前尚无有效的治疗方法或疫苗。2014年开始持续到现在，在西非国家的大暴发已导致2.8万人感染，1.1万人死亡。

针对近期开发的复制缺陷型的3型黑猩猩腺病毒为载体的埃博拉病毒疫苗(cAd3-EBO)，张其威副教授和美国乔治梅森大学Donald Seto教授在论文中指出，该疫苗是基于欧洲试验人员血清中低水平预存的抗cAd3抗体的前提上。然而，在华盛顿招募的20位接受了cAd3-EBO一期疫苗试验的参与者中，17名参与者(85%)检测出了抗cAd3的预存中和抗体;与居住在美国或泰国的人群相比，非洲人群血清中抗其它型别黑猩猩腺病毒的中和性抗体很常见，该病毒可能已从黑猩猩跨物种传播到人。因此，作者推测，非洲人群中预存的抗cAd3抗体的水平可能会比欧洲和美国更高，非洲人群中可能存在的黑猩猩腺病毒的预存免疫对疫苗临床试验来说是一个不容忽视的问题。

此外，该通讯论文也指出，由于CD8+T细胞可能在埃博拉病毒的免疫保护中发挥重要作用，而一期疫苗试验中预存的抗cAd3抗体水平和CD8+T细胞免疫应答之间是负相关关系，因此，这会减弱该疫苗的效果。作者建议，cAd3-EBO疫苗在非洲的临床试验，应当充分考虑非洲人群中存在相当高水平的抗cAd3中和抗体的可能性;对含有高或低水平抗cAd3抗体的疫苗试验者进行预分组，将有助于该疫苗效果的评价。

原文链接：

Chimpanzee Adenovirus Vector Ebola Vaccine — Preliminary Report

原文摘要：

BACKGROUND

The unprecedented 2014 epidemic of Ebola virus disease (EVD) has prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3–vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation.

METHODS

We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×1010particle units or 2×1011 particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 4 weeks after vaccination.

RESULTS

In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×1011 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×1011 particle-unit dose than in the group that received the 2×1010particle-unit dose (geometric mean titer against the Zaire antigen, 2037 vs. 331; P=0.001). Glycoprotein-specific T-Cell responses were more frequent among those who received the 2x1011 particle-unit dose than among those who received the 2×1010 particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07).

CONCLUSIONS

Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2×1011 particle-unit dose, glycoprotein Zaire–specific antibody responses were in the range reported to be associated with vaccine-induced protective immunity in challenge studies involving nonhuman primates. Clinical trials assessing cAd3-EBO are ongoing.

DOI: 10.1056/NEJMoa1410863

http://www.bio1000.com/gnjz/immunology/504723.html

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