Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial
Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial
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DOI：
10.1016/s0140-6736(05)70234-8
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发表时间：
2005-01-01
期刊：
影响因子：
168.9
通讯作者：
Hopkins, RJ
中科院分区：
文献类型：
--
作者：
Greenberg, RN;Kennedy, JS;Hopkins, RJ
背景：美国政府组织已经确定需要一种新的天花疫苗来补充已批准的小牛淋巴衍生疫苗的有限库存，这种疫苗的生产已不再被接受。我们的目的是在350名健康成年志愿者中比较新型细胞培养天花疫苗（CCSV）与小牛淋巴衍生疫苗（作为阳性对照）的安全性和免疫原性。方法在肯塔基大学医学中心进行随机对照研究。我们将150名年龄在18-30岁的牛痘新手志愿者和100名年龄在32-65岁的非牛痘新手随机分组，采用双盲方式，通过15次穿刺划伤，分别接种等量的CCSV或试验疫苗（2.5x10(5)个斑块形成单位）。免疫原性通过斑块形成（摄取率）、体液免疫反应（斑块减少中和滴度）和细胞免疫反应（痘苗特异性、干扰素γ t细胞定量、细胞毒性和t细胞增殖反应）来评估。另外100名年龄在18-30岁之间的未接种疫苗的个体以单盲方式接种了五剂CCSV中的一剂（未稀释、稀释1 / 5、1 / 10、1 / 25和1 / 50）。通过常规实验室评估、体格检查和不良事件记录来评估疫苗的安全性。主要终点是CCSV的安全性和反应原性（服用率）。350名志愿者中有349人（99.7%）出现了麻袋病变；一名接受1 / 25 CCSV稀释的未接种牛痘的个体则没有。与疫苗相关的不良事件的发生率以及体液和细胞免疫反应的程度在牛痘初始或非初始人群的疫苗组之间没有差异。CCSV在未接种疫苗的志愿者中具有免疫原性，剂量比批准的Dryvax低50倍。CCSV似乎是小牛淋巴衍生疫苗的一种安全的免疫原性替代品，对牛痘幼稚和非幼稚的人都适用。
Background US government organisations have identified the need for a new smallpox vaccine to replenish limited stocks of the approved, calf-lymph derived vaccine, the manufacture of which is no longer acceptable. We aimed to compare the safety and immunogenicity of the new cell-cultured smallpox vaccine (CCSV) to that of the calf-lymph derived vaccine (as a positive control) in 350 healthy, adult volunteers.Methods We did a randomised controlled study at the University of Kentucky Medical Center. We randomised 150 vaccinia-naive volunteers, aged 18-30 years, and 100 vaccinia-non-naive people, aged 32-65 years, to equivalent doses of either CCSV or test vaccine (2.5x10(5) plaque-forming units) by 15 puncture scarification in double-blind fashion. Immunogenicity was assessed by pock formation (take rate), humoral immune response by plaque-reduction neutralisation titres, and cellular immune response by vaccinia-specific, interferon-gamma T-cell quantification, cytotoxicity, and T-cell proliferation response. A further 100 vaccine-naive individuals, aged 18-30 years, received one of five doses of CCSV (undiluted, diluted 1 in 5, 1 in 10, 1 in 25, and 1 in 50) in single-blind fashion. Routine laboratory assessments, physical examinations, and recording of adverse events were done to assess vaccine safety. The primary endpoints were safety and reactogenicity (take rate) of CCSV.Findings 349 (99.7%) of 350 volunteers developed pock lesions; one vaccinia-naive individual who received a 1 in 25 dilution of CCSV did not. The rate of adverse events related to vaccine and the extent of humoral and cellular immune responses did not differ between the vaccine groups in vaccinia-naive or non-naive people. CCSV was immunogenic in vaccine-naive volunteers at a dose 50 times lower than that approved for Dryvax.Interpretation CCSV seems to be a safe and immunogenic alternative to calf-lymph derived vaccine for both vaccinia-naive and non-naive people.