实验性埃博拉疫苗被证实可有效保护机体免于病毒感染

  近日，发表在国际杂志Nature Medicine及New England Journal of Medicine上的两篇研究论文中，来自美国国立卫生研究院及国家过敏症和传染病研究所的研究人员通过研究开发了一种新型抑制埃博拉病毒的实验性疫苗，目前I期临床试验对20名健康成年个体进行的研究结果显示，这种新型疫苗耐受性较好及可以在机体中产生免疫系统防御能力。
  文章中，研究者Anthony S. Fauci博士指出，当前在西非肆虐的埃博拉疫情使我们不得不加大力度研发安全有效的疫苗，而新型疫苗的开发对于有效遏制埃博拉疫情的爆发和流行也至关重要。基因此前候选疫苗在人类机体中的有效数据，我们正在进行更大规模的研究来确定是否这种疫苗可以有效抑制埃博拉病毒的感染。
  埃博拉病毒的遗传物质可以通过载体病毒来进行运输，这种载体病毒比如黑猩猩机体衍生的腺病毒等，腺病毒常常会引发黑猩猩患感冒但对人类并无致病性，而候选疫苗中并不包含埃博拉病毒也并不能引发埃博拉病毒对人类的感染。试验招募的志愿者年龄在18至50岁之间，其中10名志愿者接受肌肉最小剂量候选疫苗的注射，而另外10志愿者接受最高剂量的注射，在疫苗接种后2周和4周研究人员对志愿者的血液样本进行检测来确定是否其机体产生了抗埃博拉病毒的抗体，结果显示，在接种疫苗四周内所有20名志愿者机体中均产生了抗体，而且接受高剂量疫苗注射的志愿者机体中的抗体浓度也高于低剂量疫苗注射的志愿者。
  与此同时，研究人员也分析了志愿者的血液样本来确定这种疫苗是否可以促进机体中T细胞的产生；而最新一篇研究（发表于Nature Medicine上）结果显示，注射候选疫苗的非人类灵长类动物在机体中产生了抗体和T细胞反应，这些足以保护机体免于病毒的感染。实验性的候选疫苗抵御可以诱导志愿者机体中的T细胞反应，包括产生CD8 T细胞，其对于保护机体免于埃博拉病毒感染异常重要。
  此前研究显示，在非灵长类动物中CD8 T细胞在保护动物免于病毒感染上扮演着重要角色；目前这种新型疫苗在志愿者机体中并无副作用产生。（转化医学网360zhyx.com）
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Chimpanzee Adenovirus Vector Ebola Vaccine — Preliminary Report
NEJM   DOI: 10.1056/NEJMoa1410863
Julie E. Ledgerwood, D.O., Adam D. DeZure, M.D., Daphne A. Stanley, M.S., Laura Novik, M.A., Mary E. Enama, M.A., Nina M. Berkowitz, M.P.H., Zonghui Hu, Ph.D., Gyan Joshi, M.S., Aurélie Ploquin, Ph.D., Sandra Sitar, M.S., Ingelise J. Gordon, R.N., Sarah A. Plummer, C.R.N.P., LaSonji A. Holman, F.N.P., Cynthia S. Hendel, C.R.N.P., Galina Yamshchikov, M.S., Francois Roman, M.D., Alfredo Nicosia, Ph.D., Stefano Colloca, Ph.D., Riccardo Cortese, M.D., Robert T. Bailer, Ph.D., Richard M. Schwartz, Ph.D., Mario Roederer, Ph.D., John R. Mascola, M.D., Richard A. Koup, M.D., Nancy J. Sullivan, Ph.D., Barney S. Graham, M.D., and the VRC 207 Study Team
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 2×1010 particle 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 2×1010 particle-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. (Funded by the Intramural Research Program of the National Institutes of Health; VRC 207 ClinicalTrials.gov number, NCT02231866.)

Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge