Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Vaccine. 2018 Oct 1;36(41):6183-6190. doi: 10.1016/j.vaccine.2018.08.056. Epub 2018 Aug 31.
Respiratory syncytial virus (RSV) causes respiratory disease throughout life. Here we report differences in naturally acquired immunity with age and presumed exposure.
A longitudinal, non-interventional, observational study was performed in healthy adults (20 paediatric healthcare workers and 10 non-healthcare workers), children (10 aged 3-6 years) and infants (5 aged 2-4 months and 20 aged 6-12 months). Blood samples were analysed for RSV-neutralising antibody titre, F/Ga/Gb-specific antibody titres, F-specific IgG/IgA memory B-cell frequencies and T-cell production of IFNγ, IL-4, IL-13 and IL-17.
Serum G-specific antibody titres were significantly lower in infants and children than adults. However, serum titres of F-specific and RSV-neutralising antibody and IFNγ-producing T-cell frequencies were low or absent in the infants, but comparable between children and adults. Interestingly, F-specific memory IgA B-cells could not be detected in paediatric samples and in samples from non-healthcare workers, but recordable IgA memory B-cells were found in 9/18 paediatric healthcare workers and 2/8 non-healthcare workers at the end of the RSV season. These responses waned 4-6 months later. By contrast, F-specific IgG memory B-cells were detectable in samples from all adults without significant variation across time points. T-cells producing IL-4, IL-13 and IL-17 responses were not detectable in peripheral blood from a subset of volunteers.
Repeated RSV exposure in early life generates immune responses that are inversely related to frequency of severe disease. Induction of F-specific antibody and cellular immune responses through infant vaccination might help to accelerate the development of protective immune responses at an early age. Clinicaltrials.gov reference NCT01563692 and NCT01640652.
呼吸道合胞病毒（RSV）在一生中引发呼吸道疾病。在此，我们报告了随年龄和推测的暴露而变化的自然获得性免疫差异。
对健康成年人（20 名儿科医护人员和 10 名非医护人员）、儿童（10 名 3-6 岁儿童）和婴儿（5 名 2-4 月龄和 20 名 6-12 月龄）进行了一项纵向、非干预性、观察性研究。分析了 RSV 中和抗体滴度、F/Ga/Gb 特异性抗体滴度、F 特异性 IgG/IgA 记忆 B 细胞频率以及 IFNγ、IL-4、IL-13 和 IL-17 的 T 细胞产生情况。
婴儿和儿童的血清 G 特异性抗体滴度明显低于成年人。然而，婴儿的血清 F 特异性和 RSV 中和抗体以及 IFNγ产生 T 细胞频率较低或缺失，但儿童和成年人之间无差异。有趣的是，儿科样本和非医护人员样本中无法检测到 F 特异性记忆 IgA B 细胞，但在 RSV 季节结束时，18 名儿科医护人员中有 9 人和 8 名非医护人员中有 2 人可检测到可记录的 IgA 记忆 B 细胞。这些反应在 4-6 个月后减弱。相比之下，所有成年人的样本中均可检测到 F 特异性 IgG 记忆 B 细胞，且在不同时间点之间无明显变化。部分志愿者的外周血中无法检测到产生 IL-4、IL-13 和 IL-17 反应的 T 细胞。
在生命早期反复接触 RSV 会产生与严重疾病频率呈反比的免疫反应。通过婴儿疫苗接种诱导 F 特异性抗体和细胞免疫反应可能有助于在早期加速保护性免疫反应的发展。Clinicaltrials.gov 注册号 NCT01563692 和 NCT01640652。
