Phase II, dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults ≥50 years of age
Phase II, dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults ≥50 years of age
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DOI：
10.1016/j.vaccine.2012.08.063
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发表时间：
2012-10-19
期刊：
影响因子：
5.5
通讯作者：
Risi, George
中科院分区：
文献类型：
--
作者：
Dayan, Gustavo H.;Bevilacqua, Joan;Risi, George
简介：ChimeriVax-WN 02是一种活的、减毒的嵌合疫苗，通过将编码西尼罗河病毒（NY 99株）的前膜（prM）和包膜（E）蛋白的基因插入黄热病7 D疫苗病毒中而产生，用于预防西尼罗河病毒（WNV）。这项在美国进行的II期、随机、双盲、安慰剂对照、多中心研究评估了ChimeriVax-WN 02疫苗的免疫原性、病毒血症和安全性。年龄≥ 50岁的受试者被随机分配到四个治疗组之一：ChimeriVax-WN 02 4 × 10（3）空斑形成单位（pfu）（n = 122），4 × 10（4）pfu（n = 124），4 × 10（5）pfu（n = 113）或安慰剂（n = 120）。将一个受试者子集随机分组，以评估三种不同剂量水平疫苗接种后的病毒血症。结果：在6个月的安全性随访中，WN 024 × 10（3）组共有121名受试者，WN 02 4 × 10（4）组有122名受试者，WN 02 4 × 10（5）组有110名受试者，安慰剂组有120名受试者完成了研究。通过空斑减少中和试验（PRNT）测量，在第28天，WN 02 4 x 10（3）、WN 02 4 x 10（4）和WN 02 4 x 10（5）组中分别有92.1%、93.2%和95.4%的受试者实现血清转化。病毒血症为一过性，在第2 - 14天检测到，但在第28天未检测到，并且在大多数情况下未达到定量阈值。安慰剂组和活性疫苗组中报告至少一次反应原性事件的受试者百分比相似，并且没有显示出剂量关系。结论：ChimeriVax-WN 02疫苗在所有剂量水平下在>= 50岁的受试者中具有高度免疫原性和良好的耐受性。(C)2012爱思唯尔有限公司保留所有权利。
Introduction: ChimeriVax-WN02 is a live, attenuated chimeric vaccine for protection against West Nile virus (WNV) produced by insertion of the genes encoding the pre-membrane (prM) and envelope (E) proteins of WNV (strain NY99) into the yellow fever 7D vaccine virus. This Phase II, randomized, double-blind, placebo-controlled, multi-center study in the US assessed the immunogenicity, viremia, and safety of the ChimeriVax-WN02 vaccine.Methods: The study included adults in general good health. Subjects aged >= 50 years were randomized to one of four treatment groups: ChimeriVax-WN02 4 x 10(3) plaque-forming units (pfu) (n = 122), 4 x 10(4) pfu (n = 124), 4 x 10(5) pfu (n = 113), or placebo (n = 120). A subset of subjects was randomized to assess viremia after vaccination at three different dose levels. Subjects were followed for safety up to 6 months after vaccination.Results: A total of 121subjects for WN024 x 10(3), 122 for WN02 4 x 10(4), 110 for WN02 4 x 10(5), and 120 for the placebo group completed the study up to the 6-month safety follow-up. Seroconversion, as measured by plaque reduction neutralization test (PRNT), was achieved at Day 28 by 92.1%, 93.2%, and 95.4% of subjects in the WN02 4 x 10(3), the WN02 4 x 10(4), and the WN02 4 x 10(5) groups, respectively. Viremia was transient, detected between Days 2 and 14 but not at Day 28, and in most cases did not reach the quantification threshold. The percentage of subjects reporting at least one event of reactogenicity was similar in the placebo and active vaccine groups and showed no dose relationship.Conclusions: The ChimeriVax-WN02 vaccine was highly immunogenic and well tolerated among subjects >= 50 years old at all dose levels. (C) 2012 Elsevier Ltd. All rights reserved.