Malaria: Parasites and Hosts, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France; MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at The London School of Hygiene & Tropical Medicine, Fajara, The Gambia; CIHLMU Center for International Health, Medical Center of the University of Munich, Munich, Germany.
Lancet Infect Dis. 2019 Mar;19(3):327-336. doi: 10.1016/S1473-3099(18)30674-1. Epub 2019 Feb 10.
A meningococcal group A conjugate vaccine, PsA-TT (also known as MenAfriVac), was developed with the support of the Meningitis Vaccine Project. Around 280 million individuals aged 1-29 years have been immunised across the African meningitis belt. We analysed the kinetics of vaccine-induced antibody response and assessed the possible implications for duration of protection.
We obtained data from two longitudinal studies done in The Gambia, Mali, and Senegal of antibody responses in 193 children aged 12-23 months and 604 participants aged 2-29 years following MenAfriVac vaccination. Antibodies were measured using two methods: group A serum bactericidal antibody (SBA) assay and group A-specific IgG ELISA. Data on antibody responses were analysed using a mixed-effects statistical model accounting for the mean response and variation in patterns of antibody kinetics. Determinants of antibody duration were investigated using regression analysis.
In children age 12-23 months, the reduction in MenAfriVac-induced antibody levels assessed by SBA titres had two phases: with 97·0% (95% credible interval [CrI] 95·1-98·3) of the response being short lived and decaying within the first 6 months and the remainder being long lived and decaying with a half-life of 2690 days (95% CrI 1016-15 078). Antibody levels assessed by SBA titres in participants aged 2-29 years were more persistent, with 95·0% (85·7-98·1) of the response being short lived, and the long lived phase decaying with a half-life of 6007 days (95% CrI 2826-14 279). Greater pre-vaccination antibody levels were associated with greater immunogenicity following vaccination, as well as greater antibody persistence. Despite rapid antibody declines in the first phase, antibodies in the second phase persisted at SBA titres greater than 128. Although there is no strong evidence base for a correlate of protection against infection with Neisseria meningitidis serogroup A, we use an assumed SBA titre of 128 as a threshold of protection to predict that 20 years after vaccination with a single dose of MenAfriVac, vaccine efficacy will be 52% (29-73) in children vaccinated at age 12-23 months and 70% (60-79) in participants vaccinated at age 2-29 years.
Population-level immunity induced by routine vaccination with the Expanded Programme on Immunization is predicted to persist at levels sufficient to confer more than 50% protection over a 20-year time period. Further increases in population-level immunity could be obtained via mass campaigns or by delaying the age of vaccination through the Expanded Programme on Immunization. However, the benefits of such a strategy would need to be weighed against the risks of leaving young children unvaccinated for longer.
Meningitis Vaccine Project and Institut Pasteur.
脑膜炎 A 群结合疫苗 PsA-TT（也称为 MenAfriVac）是在脑膜炎疫苗项目的支持下开发的。在非洲脑膜炎带，约有 2.8 亿 1-29 岁的人接受了免疫接种。我们分析了疫苗诱导的抗体反应的动力学，并评估了对保护持续时间的可能影响。
我们从在冈比亚、马里和塞内加尔进行的两项纵向研究中获得了数据，这些研究评估了 193 名 12-23 个月大的儿童和 604 名 2-29 岁的参与者接种 MenAfriVac 后的抗体反应。使用两种方法测量抗体：血清杀菌抗体（SBA）测定法和 A 群特异性 IgG ELISA。使用混合效应统计模型分析抗体反应数据，该模型考虑了平均反应和抗体动力学模式变化的差异。使用回归分析研究了抗体持续时间的决定因素。
在 12-23 个月大的儿童中，SBA 滴度评估的 MenAfriVac 诱导的抗体水平下降有两个阶段：97.0%（95%置信区间 [CrI] 95.1-98.3）的反应是短暂的，在头 6 个月内衰减，其余的反应是持久的，半衰期为 2690 天（95% CrI 1016-15078）。参与者 2-29 岁时 SBA 滴度评估的抗体水平更持久，95.0%（85.7-98.1）的反应是短暂的，长寿命阶段的半衰期为 6007 天（95% CrI 2826-14279）。接种前更高的抗体水平与接种后的免疫原性更强以及抗体持续时间更长有关。尽管在第一阶段抗体迅速下降，但第二阶段的抗体仍以 SBA 滴度大于 128 的水平持续存在。尽管针对 A 群脑膜炎奈瑟菌感染的保护相关性没有强有力的证据基础，但我们使用假设的 SBA 滴度 128 作为保护阈值来预测，在接种 MenAfriVac 单剂 20 年后，12-23 个月大儿童的疫苗效力将为 52%（29-73），2-29 岁儿童的疫苗效力为 70%（60-79）。
常规免疫规划接种引起的人群水平免疫力预计将持续存在足够高的水平，以在 20 年的时间内提供超过 50%的保护。通过大规模运动或通过延长免疫规划的接种年龄，可以进一步提高人群水平的免疫力。然而，需要权衡这种策略的好处与让年幼的儿童更长时间未接种疫苗的风险。
脑膜炎疫苗项目和巴斯德研究所。
