Song Joon Young, Choi Min Joo, Noh Ji Yun, Choi Won Suk, Cheong Hee Jin, Wie Seong-Heon, Lee Jin-Soo, Woo Gyu-Jin, Lee Sang Ho, Kim Woo Joo
a Division of Infectious Diseases, Department of Internal Medicine , Korea University College of Medicine , Seoul , Republic of Korea.
b Transgovernmental Enterprise for Pandemic Influenza in Korea , Seoul , Republic of Korea.
Hum Vaccin Immunother. 2017 May 4;13(5):1190-1197. doi: 10.1080/21645515.2016.1263410. Epub 2016 Dec 20.
Considering the pandemic potential of avian influenza A/H5N1, development of an effective and well-tolerated vaccine is an essential part of pandemic preparedness plans. This phase III, randomized, double-blind study was conducted to assess the immunogenicity and safety profile of an alum-adjuvanted, whole virion, pre-pandemic influenza A/H5N1 vaccine (MG1109). Healthy individuals were randomly assigned, in a 3:1 ratio, to receive two doses of either MG1109 or placebo containing alum gel. Immunogenicity was determined by hemagglutination inhibition (HI) and microneutralization (MN) assays. Solicited and unsolicited adverse events were assessed after vaccination. Among 420 enrolled subjects, 418 were available for safety analysis, and 298 MG1109 recipients were available for per-protocol immunogenicity analyses. According to the HI assays, after two vaccine doses, all three of the Committee for Medicinal Products for Human Use (CHMP) criteria were met against the vaccine strain for all age groups: seroprotection rate = 74.8% (95% CI: 69.9 - 79.8), seroconversion rate = 67.8% (95% CI: 62.5-73.1), and geometric mean titer ratio (GMTR) = 5.9 (95% CI: 5.4 - 6.4). According to the MN assays, the GMTR was 2.4 (95% CI: 2.1 - 2.7) and 7.0 (95% CI: 6.3 - 7.9) three weeks after the first and second vaccine doses, respectively. Solicited local and systemic adverse events were mostly mild to moderate and were not significantly different between MG1109 and placebo recipients. In conclusion, two-dose administration of alum-adjuvanted H5N1 pre-pandemic influenza vaccine (MG1109) was highly immunogenic and tolerable in adults.
鉴于甲型H5N1禽流感的大流行潜力,研发一种有效且耐受性良好的疫苗是大流行防范计划的重要组成部分。本III期随机双盲研究旨在评估一种含铝佐剂的全病毒大流行前甲型H5N1流感疫苗(MG1109)的免疫原性和安全性。健康个体按3:1的比例随机分配,分别接受两剂MG1109或含铝凝胶的安慰剂。通过血凝抑制(HI)和微量中和(MN)试验测定免疫原性。接种疫苗后评估预期和非预期不良事件。在420名入组受试者中,418名可进行安全性分析,298名MG1109接种者可进行符合方案的免疫原性分析。根据HI试验,两剂疫苗接种后,所有年龄组针对疫苗株均满足人用药品委员会(CHMP)的所有三项标准:血清保护率=74.8%(95%CI:69.9 - 79.8),血清转化率=67.8%(95%CI:62.5 - 73.1),几何平均滴度比(GMTR)=5.9(95%CI:5.4 - 6.4)。根据MN试验,首次和第二次疫苗接种后三周的GMTR分别为2.4(95%CI:2.1 - 2.7)和7.0(95%CI:6.3 - 7.9)。预期的局部和全身不良事件大多为轻至中度,MG1109接种者和安慰剂接种者之间无显著差异。总之,两剂含铝佐剂的H5N1大流行前流感疫苗(MG1109)在成人中具有高度免疫原性且耐受性良好。