Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands.
Expanded Programme on Immunization, Department of Immunization, Vaccines, and Biologicals, World Health Organization, Geneva, Switzerland.
Lancet Infect Dis. 2019 Nov;19(11):1246-1254. doi: 10.1016/S1473-3099(19)30396-2. Epub 2019 Sep 20.
Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related morbidity and mortality. However, there is concern that early vaccination might blunt the immune response to subsequent measles vaccine doses. We systematically reviewed the available evidence on the effect of MCV1 administration to infants younger than 9 months on their immune responses to subsequent MCV doses.
For this systematic review and meta-analysis, we searched for randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We included studies reporting data on strength or duration of humoral and cellular immune responses, and on vaccine efficacy or vaccine effectiveness after two-dose or three-dose MCV schedules. Our outcome measures were proportion of seropositive infants, geometric mean titre, vaccine efficacy, vaccine effectiveness, antibody avidity index, and T-cell stimulation index. We used random-effects meta-analysis to derive pooled estimates of the outcomes, where appropriate. We assessed the methodological quality of included studies using Grading of Recommendation Assessment, Development and Evaluation (GRADE) guidelines.
Our search retrieved 1156 records and 85 were excluded due to duplication. 1071 records were screened for eligibility, of which 351 were eligible for full-text screening and 21 were eligible for inclusion in the review. From 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI 96-99; I=79·8%, p<0·0001), which was not significantly different from seropositivity after a two-dose MCV schedule starting later (p=0·087). Only one of four studies found geometric mean titres after MCV2 administration to be significantly lower when MCV1 was administered before 9 months of age than at 9 months of age or later. There was insufficient evidence to determine an effect of age at MCV1 administration on antibody avidity. The pooled vaccine effectiveness estimate derived from two studies of a two-dose MCV schedule with MCV1 vaccination before 9 months of age was 95% (95% CI 89-100; I=12·6%, p=0·29). Seven studies reporting on measles virus-specific cellular immune responses found that T-cell responses and T-cell memory were sustained, irrespective of the age of MCV1 administration. Overall, the quality of evidence was moderate to very low.
Our findings suggest that administering MCV1 to infants younger than 9 months followed by additional MCV doses results in high seropositivity, vaccine effectiveness, and T-cell responses, which are independent of the age at MCV1, supporting the vaccination of very young infants in high-risk settings. However, we also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older. The clinical and public-health relevance of this immunity blunting effect are uncertain.
WHO.
在高风险环境中，为 9 个月以下婴儿接种一剂麻疹疫苗（MCV1），有可能降低麻疹相关发病率和死亡率。然而，人们担心早期接种可能会削弱对后续麻疹疫苗剂量的免疫反应。我们系统地回顾了现有关于在 9 个月以下婴儿中接种 MCV1 对随后接种 MCV 剂量的免疫反应影响的证据。
在本次系统综述和荟萃分析中，我们检索了随机和准随机对照试验、暴发调查以及队列和病例对照研究，没有对发表日期进行限制，这些研究中都为 9 个月以下婴儿接种了 MCV1。我们于 2015 年 6 月 2 日进行文献检索，并于 2019 年 1 月 14 日更新。我们纳入了报告两剂或三剂 MCV 接种后体液和细胞免疫反应强度或持续时间以及疫苗效力或疫苗效果数据的研究。我们的结局指标是血清阳性婴儿的比例、几何平均滴度、疫苗效力、疫苗效果、抗体亲和指数和 T 细胞刺激指数。我们使用随机效应荟萃分析来推导出适当的汇总估计值。我们使用推荐评估、制定与评估（GRADE）指南来评估纳入研究的方法学质量。
我们的检索共检索到 1156 条记录，其中 85 条因重复而被排除。对 1071 条记录进行了资格筛选，其中 351 条符合全文筛选标准，21 条符合纳入本综述的标准。在 13 项研究中，在接种两剂 MCV 疫苗时，9 个月以下婴儿接种两剂 MCV1 的血清阳性比例为 98%（95%CI 96-99；I=79.8%，p<0.0001），与较晚开始的两剂 MCV 方案（p=0.087）相比，这并没有显著差异。只有四项研究中的一项发现，当 MCV1 在 9 个月之前接种时，MCV2 接种后的几何平均滴度显著低于 9 个月或更晚时接种。尚没有足够的证据来确定 MCV1 接种年龄对抗体亲和性的影响。从两项在 9 个月之前接种 MCV1 的两剂 MCV 接种方案中得出的疫苗效力估计值为 95%（95%CI 89-100；I=12.6%，p=0.29）。7 项报告麻疹病毒特异性细胞免疫反应的研究发现，T 细胞反应和 T 细胞记忆得到了维持，无论 MCV1 的接种年龄如何。总的来说，证据质量为中等至极低。
我们的研究结果表明，在 9 个月以下婴儿中接种 MCV1 后再接种额外的 MCV 疫苗会导致高血清阳性率、疫苗效力和 T 细胞反应，而这与 MCV1 的接种年龄无关，支持在高风险环境中为非常年幼的婴儿接种疫苗。然而，我们也发现一些证据表明，在 9 个月以下婴儿中接种 MCV1 后，与在 9 个月或更大年龄开始麻疹疫苗接种相比，在接种一剂或两剂 MCV 后，抗体滴度较低。这种免疫减弱效应的临床和公共卫生相关性尚不确定。
世界卫生组织。
