Evaluation of safety and immunogenicity of HNVAC, an MDCK-based H1N1 pandemic influenza vaccine, in Phase I single centre and Phase II/III multi-centre, double-blind, randomized, placebo-controlled, parallel assignment studies
Evaluation of safety and immunogenicity of HNVAC, an MDCK-based H1N1 pandemic influenza vaccine, in Phase I single centre and Phase II/III multi-centre, double-blind, randomized, placebo-controlled, parallel assignment studies
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DOI：
10.1016/j.vaccine.2014.05.039
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发表时间：
2014-07-31
期刊：
影响因子：
5.5
通讯作者：
Ella, Krishna M.
中科院分区：
文献类型：
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作者：
Basavaraj, V. H.;Sampath, G.;Ella, Krishna M.
报告了以MDCK为基础的H1N1大流行性流感疫苗HNVAC在18-65岁成年人中的临床评价。在第一阶段随机、双盲、安慰剂对照、单中心研究中，160名受试者被平行分配为3：1的疫苗：安慰剂组(n=60：20)，同时使用氢氧化铝佐剂和非佐剂疫苗配方。含有15mU血凝素蛋白的两种制剂单次给药的不良反应都很小，最常见的不良反应是注射部位疼痛(11.67%)和发热(10.00%)。两种配方都产生了74-81%的血清保护率(SRP：滴度=40)，67-70%的血清转化率(SRC：0至21天滴度增加了四倍)，几何平均滴度(GMT)增加了四倍。氢氧化铝对免疫原性和反应性均无明显影响。然而，基于其对许多疫苗的稳定性和免疫原性的公认的积极作用，以及其在HNVAC临床前和第一阶段研究中的边际效益，明矾佐剂HNVAC进一步在交错的II/III阶段随机、双盲、安慰剂对照、多中心研究中进行测试，分别有200名和195名受试者，4：1平行分配到佐剂疫苗组和安慰剂组。在这些研究中，最常见的不良反应是注射部位的疼痛(第一阶段和第二阶段分别为6.88%和5.77%)和发热(分别为7.50%和7.05%)，单次给药导致87-90%的SRP，85-86%的SRC，GMT增加近6倍，达到或超过许可标准。结论：HNVAC对18~65岁成人是安全的，具有免疫原性。(C)2014爱思唯尔有限公司。保留所有权利。
The clinical evaluation of the MDCK-based H1N1 pandemic influenza vaccine HNVAC in adults aged 18-65 years is reported. In the Phase I randomized, double-blind, placebo-controlled, single-centre study, 160 subjects were parallelly assigned 3:1 to vaccine:placebo groups (n = 60:20) with both the aluminium hydroxide adjuvanted and non-adjuvanted vaccine formulations. A single dose of both the formulations containing 15 mu g of haemagglutinin protein showed minimal adverse reactions, the most common of which were pain at injection site (11.67%) and fever (10.00%). Both formulations produced 74-81% seroprotection (SRP: titre of >= 40), 67-70% seroconversion (SRC: four-fold increase in titres between days 0 and 21), and a four-fold increase in geometric mean titres (GMT). Aluminium hydroxide did not have a significant effect either on immunogenicity or on reactogenicity. Nevertheless, based on its recognized positive effects on the stability and immunogenicity of many vaccines, and its marginal benefit in both pre-clinical and Phase I studies of HNVAC, alum adjuvanted HNVAC was further tested in a staggered Phase II/III randomized, double-blind, placebo-controlled, multi-centre study of 200 and 195 subjects, respectively, parallelly assigned 4:1 to adjuvanted vaccine and placebo groups. In these studies, the most common adverse reactions were pain at injection site (6.88% and 5.77% in Stage 1 and Stage 2, respectively) and fever (7.50% and 7.05%, respectively), and a single dose resulted in 87-90% SRP, 85-86% SRC, and a nearly six-fold increase in GMT, meeting or exceeding licensing criteria. It is concluded that HNVAC is safe and immunogenic to adults of 18-65 years. (C) 2014 Elsevier Ltd. All rights reserved.