新型口服脊髓灰质炎病毒2型疫苗和沙宾单价口服脊髓灰质炎病毒2型疫苗诱导的肠道黏膜免疫反应：四项临床试验数据分析
Intestinal mucosal immune responses induced by novel oral poliovirus vaccine type 2 and Sabin monovalent oral poliovirus vaccine type 2: an analysis of data from four clinical trials.
作者信息
Godin Audrey, Brickley Elizabeth B, Connor Ruth I, Wieland-Alter Wendy F, Ackerman Margaret E, Weiner Joshua A, Modlin John, Arita Minetaro, Bandyopadhyay Ananda S, Gast Chris, Sáez-Llorens Xavier, Rüttimann Ricardo W, Van Damme Pierre, De Coster Ilse, Wright Peter F
机构信息
Health Equity Action Lab, Department of Infectious Disease Epidemiology and International Health, London School of Hygiene & Tropical Medicine, London, UK.
Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth Health, Lebanon, NH, USA.
出版信息
Lancet Microbe. 2025 Jun;6(6):101028. doi: 10.1016/j.lanmic.2024.101028. Epub 2025 Apr 30.
BACKGROUND
A novel oral polio vaccine type 2 (nOPV2), which is more genetically stable (ie, lower risks of reverting to neurovirulence) than the Sabin monovalent OPV2 (mOPV2), has been deployed to interrupt circulating vaccine-derived poliovirus type 2 (PV2) outbreaks. This study compares intestinal mucosal immune responses induced by nOPV2 and mOPV2.
METHODS
In this analysis, we evaluated intestinal mucosal immune responses in healthy participants of different ages (ie, infants aged 18-22 weeks, children aged 1-4 years, and adults aged 18-50 years) and vaccine backgrounds (ie, OPV2-experienced vs OPV2-naive). Participants were selected from two phase 2 trials of nOPV2, conducted in 2018-19 (infants and children, NCT03554798 [Panama]; adults, EudraCT 2018-001684-22-NCT04544787 [Belgium]), and two phase 4 historical control trials of mOPV2, conducted in 2015-16 (infants and children, NCT02521974 [Panama]; adults, EudraCT 2015-003325-33 [Belgium]). We measured PV2-specific neutralising activity and IgA concentrations in stools collected before and 14 days after vaccination.
FINDINGS
We compared data from 160 participants (ie, 47 infants, 47 children, and 66 adults) in the nOPV2 trials to 188 participants (ie, 42 infants, 46 children, and 100 adults) in the mOPV2 trials. Within each age group, one dose of nOPV2 or mOPV2 induced similar intestinal PV2-specific neutralisation and IgA responses on day 14. Responses diminished with age: among the OPV2-naive participants who received nOPV2, 27 (82%) of 33 infants, 17 (61%) of 28 children, and four (25%) of 16 adults had detectable PV2-specific neutralisation on day 14. Despite having similar median log IgA responses (1·4 [IQR 1·0-2·2] vs 1·4 [1·1-1·7], p=0·34) and median log neutralisation titres (1 [IQR 1-1] vs 1 [1-1·5], p=0·89) on day 14, a smaller percentage of OPV2-experienced adults shed vaccine virus than OPV2-naive adults upon nOPV2 challenge (20% vs 82%, p<0·0001).
INTERPRETATION
We found no evidence of differences in the intestinal mucosal immune responses induced by nOPV2 or Sabin mOPV2 and observed the strongest responses in infants.
FUNDING
The Bill & Melinda Gates Foundation, Japan Agency for Medical Research and Development.
背景
一种新型口服脊髓灰质炎2型疫苗（nOPV2）已被用于阻断疫苗衍生脊髓灰质炎2型病毒（PV2）的传播，该疫苗在基因上比单价口服脊髓灰质炎2型疫苗（mOPV2）更稳定（即恢复神经毒性的风险更低）。本研究比较了nOPV2和mOPV2诱导的肠道黏膜免疫反应。
方法
在本分析中，我们评估了不同年龄（即18 - 22周龄婴儿、1 - 4岁儿童和18 - 50岁成年人）和疫苗接种史（即有OPV2接种史与无OPV2接种史）的健康参与者的肠道黏膜免疫反应。参与者选自2018 - 2019年进行的两项nOPV2 2期试验（婴儿和儿童，NCT03554798[巴拿马]；成年人，EudraCT 2018 - 001684 - 22 - NCT04544787[比利时]），以及2015 - 2016年进行的两项mOPV2 4期历史对照试验（婴儿和儿童，NCT02521974[巴拿马]；成年人，EudraCT 2015 - 003325 - 33[比利时]）。我们测量了接种疫苗前和接种后14天收集的粪便中PV2特异性中和活性和IgA浓度。
结果
我们将nOPV2试验中的160名参与者（即47名婴儿、47名儿童和66名成年人）的数据与mOPV2试验中的188名参与者（即42名婴儿、46名儿童和100名成年人）的数据进行了比较。在每个年龄组中，一剂nOPV2或mOPV2在第14天诱导的肠道PV2特异性中和和IgA反应相似。反应随年龄增长而减弱：在接受nOPV2的无OPV2接种史参与者中，33名婴儿中的27名（82%）、28名儿童中的17名（61%）和16名成年人中的4名（25%）在第14天有可检测到的PV2特异性中和。尽管在第14天的IgA反应中位数对数（1.4[四分位间距1.0 - 2.2]对1.4[1.1 - 1.7]，p = 0.34）和中和滴度中位数对数（1[四分位间距1 - 1]对1[1 - 1.5]，p = 0.89）相似，但在nOPV2激发后，有OPV2接种史的成年人排出疫苗病毒的比例低于无OPV2接种史的成年人（20%对82%，p < 0.0001）。
解读
我们没有发现nOPV2或Sabin mOPV2诱导的肠道黏膜免疫反应存在差异的证据，并且观察到婴儿的反应最强。
资助
比尔及梅琳达·盖茨基金会、日本医疗研究与开发机构。
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