Department of Clinical Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Ratchathewi, Bangkok 10400, Thailand.
Vaccine. 2013 Mar 1;31(11):1503-9. doi: 10.1016/j.vaccine.2012.12.082. Epub 2013 Jan 11.
Emergence and rapid spread of influenza H1N1 virus prompted health authorities to develop a safe and effective influenza vaccine for domestic use. The Thai Government Pharmaceutical Organization (GPO) with technical support from Russia through WHO had prepared a pandemic live attenuated vaccine (PLAIV) using ca-ts attenuated candidate strain A/17/CA/2009/38 (H1N1) for Thais.
Each participant received two doses of intranasal H1N1 vaccine or placebo 21 days apart. All were followed up at 7, 21, 42 and 60 days after first immunization. Blood was drawn for hemagglutination inhibition (HAI) assay from all participants at days 1, 21, 42, and 60 after first immunization. A subset of 40 participants aged 19-49 years was randomly selected for nasal washing at days 1, 21, 42, and 60 to assess IgA using direct enzyme-linked immunosorbent assay (ELISA) along with serum HAI and microneutralization (MN) assay determination.
A total of 363 subjects aged 12-75 years were randomized into 2 groups (271 vaccinees:92 placebos). Almost all AEs were mild to moderate. Local reactions were stuffy nose (22.3%), runny nose (25.1%), scratchy throat (27.2%) and sore throat (19.3%). Systemic reactions included headache (21.7%), myalgia (13.8%), fatigue (16.8%) and postnasal drip (19.9%). On day 60, HAI seroconversion rates for vaccine:placebo group were 30.3:6.0 for ITT and 29.4:5.1 for PP analysis. Children showed highest seroconversion rate at 44, but it decreased to 39.4 when all 3 assays (HAI, MN assay and ELISA) from subgroup analysis were considered.
The vaccine candidate is safe. The use of more than one assay may be needed for evaluation of immune response because live attenuated vaccines could effectively induce different kinds of responses. Different individuals could also mount different kinds of immune response, even to the same antigen.
甲型 H1N1 流感病毒的出现和迅速传播促使卫生当局为国内使用研制安全有效的流感疫苗。在世界卫生组织的技术支持下，泰国政府制药组织（GPO）使用 ca-ts 减毒候选株 A/17/CA/2009/38（H1N1）为泰国人制备了一种大流行性减毒活疫苗（PLAIV）。
每位参与者接受两次鼻内接种 H1N1 疫苗或安慰剂，间隔 21 天。所有参与者均在首次免疫后 7、21、42 和 60 天进行随访。所有参与者在首次免疫后第 1、21、42 和 60 天采血进行血凝抑制（HAI）检测。从 19-49 岁的 40 名参与者中随机选择一部分进行鼻冲洗，在第 1、21、42 和 60 天使用直接酶联免疫吸附试验（ELISA）评估 IgA，同时进行血清 HAI 和微量中和（MN）试验测定。
共有 363 名 12-75 岁的受试者被随机分为 2 组（271 名疫苗接种者：92 名安慰剂）。几乎所有的不良事件均为轻度至中度。局部反应包括鼻塞（22.3%）、流鼻涕（25.1%）、喉咙发痒（27.2%）和喉咙痛（19.3%）。全身反应包括头痛（21.7%）、肌痛（13.8%）、疲劳（16.8%）和鼻后滴注（19.9%）。在第 60 天，疫苗接种者的 HAI 血清转化率：安慰剂组为 ITT30.3:6.0，PP 分析为 29.4:5.1。儿童的血清转化率最高为 44，但当从亚组分析中考虑到所有 3 种检测（HAI、MN 检测和 ELISA）时，血清转化率下降至 39.4。
候选疫苗是安全的。由于减毒活疫苗可以有效诱导不同类型的反应，因此可能需要使用多种检测方法来评估免疫反应。即使使用相同的抗原，不同的个体也可能产生不同类型的免疫反应。
