葛兰素史克埃博拉疫苗临床一期表现良好

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熟悉医药产业的人们可能都会记得2014年发生在西非的那场埃博拉疫情。这次疫情造成了数以千计的人死于非命。时隔一年，这场疫情已经渐渐平息下去，但是医药研发人员开发开发埃博拉疫苗的脚步却丝毫没有停下。最近，葛兰素史克公司宣布公司开发的埃博拉疫苗一期临床研究已经取得良好结果。疫苗在成年人身上表现出了良好的相容性和很强的免疫反应。

这次临床一期研究是在美国和马里进行的。研究人员分别在美国巴尔地摩和马里招募了20名（18岁-65岁）和91名（18-50）志愿者进行测试。同时研究人员还检测这一疫苗与Emergent BioSolutions公司的激活剂产品联用效果。这一研究目前已经被发表在The Lancet Infectious Disease杂志上。GSK的合作者马里兰大学医学院疫苗研发中心的研究人员表示在试验中未发现明显的安全问题。而此前，GSK的疫苗已经在塞内加尔和利比里亚分别进行了临床二期和临床三期研究。

除了GSK以外，许多其他公司也都在这一领域取得可喜进展。Profectus BioSciences开发的三价埃博拉疫苗已经在猴子实验中取得成功，并将于2016年年中进入临床研究；默沙东公司和NewLink的产品也已经取得不小进展，获得了政府2600万美元的资助。

虽然，为了攻克埃博拉病毒，世界各国政府和医药企业都付出了巨大努力。但是在研究人员面前还是有不小的阻碍。首先就是很难招募到患有这种疾病的患者，甚至很难取得患者身上的样本。因为尽管此次埃博拉疫情非常严重，但整体而言，埃博拉病毒的传播都是十分有限的；此外埃博拉患者一旦死亡，其遗体会被迅速活化以免病毒的进一步扩散。这些都给疫苗的测试带来困难。另一个问题就是，目前埃博拉病毒的起源仍不清楚，尽管大多数科学家认为蝙蝠是其源宿主，但是如果无法确定其源宿主，将很难划分适用人群。为此，目前FDA也正在考虑给埃博拉疫苗审批以特殊审批通道。

来源：生物谷

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Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial

Milagritos D Tapia, MD†, Prof Samba O Sow, MD†, Kirsten E Lyke, MD†, Fadima Cheick Haidara, MD, Fatoumata Diallo, MD, Moussa Doumbia, MD, Awa Traore, PharmD, Flanon Coulibaly, MD, Mamoudou Kodio, PharmD, Uma Onwuchekwa, BS, Prof Marcelo B Sztein, MD, Rezwanul Wahid, PhD, Prof James D Campbell, MD, Marie-Paule Kieny, PhD, Vasee Moorthy, DPhil, Egeruan B Imoukhuede, MBBS, Tommy Rampling, MRCP, Francois Roman, MD, Iris De Ryck, MD, Abbie R Bellamy, PhD, Len Dally, MS, Olivier Tshiani Mbaya, MD, Aurélie Ploquin, PhD, Yan Zhou, PhD, Daphne A Stanley, MS, Robert Bailer, PhD, Richard A Koup, MD, Mario Roederer, PhD, Julie Ledgerwood, DO, Prof Adrian V S Hill, DM, W Ripley Ballou, MD, Nancy Sullivan, PhD, Barney Graham, MD, Prof Myron M Levine, MD

Background
The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo).

Methods
In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18–65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18–50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 1010 viral particle units (pu), 2·5 × 1010 pu, 5 × 1010 pu, or 1 × 1011 pu; US participants received 1 × 1010 pu or 1 × 1011 pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 108 plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian).

Findings
Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 × 1010 pu, 35 [38%] to 2·5 × 1010 pu, 35 [38%] to 5 × 1010 pu, and 11 [12%] to 1 × 1011 pu) and 20 in the USA (ten [50%] to 1 × 1010 pu and ten [50%] to 1 × 1011 pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 × 1010 and two [2%] received 1 × 1011 pu) and four (20%) of 20 in the USA (all received 1 × 1011 pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness.

Interpretation
1 × 1011 pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers).

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00362-X/fulltext