Jain Varsha K, Domachowske Joseph B, Wang Long, Ofori-Anyinam Opokua, Rodríguez-Weber Miguel A, Leonardi Michael L, Klein Nicola P, Schlichter Gary, Jeanfreau Robert, Haney Byron L, Chu Laurence, Harris Jo-Ann S, Sarpong Kwabena O, Micucio Amanda C, Soni Jyoti, Chandrasekaran Vijayalakshmi, Li Ping, Innis Bruce L
GSK Vaccines, King of Prussia, Pennsylvania.
SUNY Upstate Medical University, Syracuse, New York.
J Pediatric Infect Dis Soc. 2017 Mar 1;6(1):9-19. doi: 10.1093/jpids/piw068.
BACKGROUND.: Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose.
METHODS.: We compared the only United States-licensed standard-dose IIV4 (0.25 mL, 7.5 µg hemagglutinin per influenza strain) versus double-dose IIV4 manufactured by a different process (0.5 mL, 15 µg per strain) in a phase III, randomized, observer-blind trial in children 6-35 months of age (NCT02242643). The primary objective was to demonstrate immunogenic noninferiority of the double-dose for all vaccine strains 28 days after last vaccination. Immunogenic superiority of the double-dose was evaluated post hoc. Immunogenicity was assessed in the per-protocol cohort (N = 2041), and safety was assessed in the intent-to-treat cohort (N = 2424).
RESULTS.: Immunogenic noninferiority of double-dose versus standard-dose IIV4 was demonstrated in terms of geometric mean titer (GMT) ratio and seroconversion rate difference. Superior immunogenicity against both vaccine B strains was observed with double-dose IIV4 in children 6-17 months of age (GMT ratio = 1.89, 95% confidence interval [CI] = 1.64-2.17, B/Yamagata; GMT ratio = 2.13, 95% CI = 1.82-2.50, B/Victoria) and in unprimed children of any age (GMT ratio = 1.85, 95% CI = 1.59-2.13, B/Yamagata; GMT ratio = 2.04, 95% CI = 1.79-2.33, B/Victoria). Safety and reactogenicity, including fever, were similar despite the higher antigen content and volume of the double-dose IIV4. There were no attributable serious adverse events.
CONCLUSIONS.: Double-dose IIV4 may improve protection against influenza B in some young children and simplifies annual influenza vaccination by allowing the same vaccine dose to be used for all eligible children and adults.
3岁以下儿童可能从双倍剂量的四价流感灭活疫苗（IIV4）而非标准剂量中获益。
在一项针对6至35个月大儿童的III期随机、观察者盲法试验（NCT02242643）中，我们比较了美国唯一获批的标准剂量IIV4（0.25 mL，每株流感病毒血凝素7.5 µg）与通过不同工艺生产的双倍剂量IIV4（0.5 mL，每株15 µg）。主要目标是证明在最后一次接种后28天，双倍剂量对所有疫苗株的免疫原性非劣效性。事后评估了双倍剂量的免疫原性优越性。在符合方案队列（N = 2041）中评估免疫原性，在意向性治疗队列（N = 2424）中评估安全性。
在几何平均滴度（GMT）比值和血清转化率差异方面，证明了双倍剂量IIV4相对于标准剂量IIV4的免疫原性非劣效性。在6至17个月大的儿童中（GMT比值 = 1.89，95%置信区间[CI] = 1.64 - 2.17，B/山形株；GMT比值 = 2.13，95%CI = 1.82 - 2.50，B/维多利亚株）以及任何年龄的未接种过疫苗的儿童中（GMT比值 = 1.85，95%CI = 1.59 - 2.13，B/山形株；GMT比值 = 2.04，95%CI = 1.79 - 2.33，B/维多利亚株），观察到双倍剂量IIV4对两种B型疫苗株具有更高的免疫原性。尽管双倍剂量IIV4的抗原含量和体积更高，但安全性和反应原性，包括发热，是相似的。没有可归因的严重不良事件。
双倍剂量IIV4可能会改善对一些幼儿的流感B型保护，并通过允许对所有符合条件的儿童和成人使用相同的疫苗剂量来简化年度流感疫苗接种。
