Duke Global Health Institute, Duke University, Trent Hall, 310 Trent Drive, Durham, NC 27710, USA.
Fogarty International Center/National Institutes of Health, Bethesda, MD, USA.
Vaccine. 2019 Jan 7;37(2):352-365. doi: 10.1016/j.vaccine.2018.05.080. Epub 2018 Nov 12.
Immunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3.
Polio neutralizing antibody assays were conducted at 7 and 15 months of age for serotypes 1 and 3. Analyses were conducted on children receiving ≥3 OPV doses (n = 1449). History of vaccination, feeding patterns, physical growth, home environment, diarrhea, enteropathogen detection, and gut inflammation were examined as risk factors for non-response [Log(titer) < 3] and Log(titer) by serotype using multivariate regression.
Serotype 1 seroconversion was significantly higher than serotype 3 (96.6% vs. 89.6%, 15 months). Model results indicate serotypes 1 and 3 failure was minimized following four and six OPV doses, respectively; however, enteropathogen detection and poor socioeconomic conditions attenuated response in both serotypes. At three months of age, bacterial detection in stool reduced serotype 1 and 3 Log titers by 0.34 (95% CI 0.14-0.54) and 0.53 (95% CI 0.29-0.77), respectively, and increased odds of serotype 3 failure by 3.0 (95% CI 1.6-5.8). Our socioeconomic index, consisting of Water, Assets, Maternal education, and Income (WAMI), was associated with a 0.79 (95% CI 0.15-1.43) and 1.23 (95% CI 0.34-2.12) higher serotype 1 and 3 Log titer, respectively, and a 0.04 (95% CI 0.002-0.40) lower odds of serotype 3 failure. Introduction of solids, transferrin receptor, and underweight were differentially associated with serotype response. Other factors, including diarrheal frequency and breastfeeding practices, were not associated with OPV response.
Under real-world conditions, improved vaccination coverage and socio-environmental conditions, and reducing early life bacterial exposures are key to improving OPV response and should inform polio eradication strategies.
免疫规划利用了几十年的研究成果，以最大限度地提高口服脊髓灰质炎疫苗（OPV）的效果。为了实现全球消灭脊髓灰质炎的目标，世界卫生组织（WHO）于 2012 年建议逐步用脊灰病毒灭活疫苗（IPV）替代 OPV。本研究利用 MAL-ED 前瞻性出生队列数据，通过测量血清型 1 和 3 的 OPV 反应，评估了影响 OPV 免疫的早期生活暴露因素。
在 7 个月和 15 个月时，对血清型 1 和 3 进行脊灰中和抗体检测。分析了接受≥3 剂 OPV 疫苗的儿童（n=1449）的数据。接种史、喂养方式、体格生长、家庭环境、腹泻、肠道病原体检测和肠道炎症被视为非应答（Log(titer)＜3）和血清型应答的危险因素，使用多变量回归进行分析。
血清型 1 的血清转化率明显高于血清型 3（96.6%比 89.6%，15 个月）。模型结果表明，分别接种四剂和六剂 OPV 疫苗后，血清型 1 和 3 的失败率最低；然而，肠道病原体检测和较差的社会经济条件会减弱两种血清型的反应。在 3 个月大时，粪便中细菌的检测使血清型 1 和 3 的 Log 滴度分别降低了 0.34（95%CI 0.14-0.54）和 0.53（95%CI 0.29-0.77），使血清型 3 失败的几率分别增加了 3.0（95%CI 1.6-5.8）倍。我们的社会经济指数（由水、资产、母亲教育和收入（WAMI）组成）与血清型 1 和 3 的 Log 滴度分别相关，分别增加了 0.79（95%CI 0.15-1.43）和 1.23（95%CI 0.34-2.12），而血清型 3 失败的几率降低了 0.04（95%CI 0.002-0.40）。固体食物的引入、转铁蛋白受体和体重不足与血清型反应呈不同的相关性。其他因素，包括腹泻频率和母乳喂养方式，与 OPV 反应无关。
在现实条件下，提高疫苗接种覆盖率和社会环境条件，减少早期生活中的细菌暴露，是提高 OPV 反应的关键，应纳入脊灰消灭策略。
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