印度农村地区儿童中减毒活疫苗和灭活流感疫苗的效果：一项为期 2 年的随机、三盲、安慰剂对照试验。
Efficacy of live attenuated and inactivated influenza vaccines among children in rural India: A 2-year, randomized, triple-blind, placebo-controlled trial.
机构信息
Centre for Community Medicine, All India Institute of Medical Sciences, Delhi, India.
Microbiology Department, All India Institute of Medical Sciences, Delhi, India.
出版信息
PLoS Med. 2021 Apr 29;18(4):e1003609. doi: 10.1371/journal.pmed.1003609. eCollection 2021 Apr.
BACKGROUND
Influenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years.
METHODS AND FINDINGS
In June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV (n = 1,015), IIV (n = 1,010), nasal placebo (n = 507), or IPV (n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years. Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year. In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was -46.2% (95% CI -88.9 to -13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI -19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted.
CONCLUSIONS
In this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children.
TRIAL REGISTRATION
Clinical Trials Registry of India CTRI/2015/06/005902.
背景
流感是印度发热性急性呼吸道感染（FARI）的一个病因；然而，在印度进行的流感疫苗试验却很少。我们通过在印度农村地区进行的一项为期 2 年的随机、三盲、安慰剂对照试验，评估了减毒活流感疫苗（LAIV）和灭活流感疫苗（IIV）在 2 至 10 岁儿童中的绝对和相对疗效。
方法和发现
2015 年 6 月，儿童按照 2:2:1:1 的比例随机分配至 LAIV、IIV、鼻内安慰剂或灭活脊髓灰质炎疫苗（IPV）组。2016 年 6 月，按照原始分组进行了重复接种。总体而言，共有 3041 名儿童接受了 LAIV（n=1015）、IIV（n=1010）、鼻内安慰剂（n=507）或 IPV（n=509）。儿童的平均年龄为 6.5 岁，其中 20%为 9 至 10 岁。通过每周的家庭访视，从患有 FARI 的儿童中采集鼻和咽喉拭子，并通过聚合酶链反应检测流感病毒。主要结局是经实验室确认的流感相关 FARI；采用 Cox 比例风险模型（PH）进行改良意向治疗（mITT）分析计算疫苗有效性（VE），用于每年分析。在第 1 年，LAIV 的 VE 为 40.0%（95%置信区间（CI）25.2 至 51.9），IIV 的 VE 为 59.0%（95%CI 47.8 至 67.9），与对照组相比；LAIV 与 IIV 相比的相对疗效为-46.2%（95%CI-88.9 至-13.1）。在第 2 年，LAIV 的 VE 为 51.9%（95%CI 42.0 至 60.1），IIV 的 VE 为 49.9%（95%CI 39.2 至 58.7）；LAIV 与 IIV 相比的相对疗效为 4.2%（95%CI-19.9 至 23.5）。未报告严重的与疫苗相关的不良事件。研究局限性包括：第 1 年鼻内疫苗和注射疫苗对儿童的剂量要求不同（LAIV 为单剂，IIV 为 2 剂），以及未进行免疫原性研究。
结论
在这项研究中，我们发现 LAIV 和 IIV 疫苗在印度儿童中是安全且对流感病毒感染具有中等疗效的。
临床试验注册
印度临床试验注册中心 CTRI/2015/06/005902。
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