英国引入轮状病毒疫苗前后不同年龄组对轮状病毒感染的免疫力及疾病风险:一项观察性血清流行病学研究。

Age-specific immunity to rotavirus infection and the risk of disease before and after rotavirus vaccine introduction in the United Kingdom: an observational, seroepidemiological study.

作者信息

Hungerford Daniel, Pitzer Virgina E, Jere Khuzwayo C, Henrion Marc Y R, Mandolo Jonathan, Beavis Catherine, Ryan Karen, Lowe Jenna, Cunliffe Nigel A, French Neil, Iturriza-Gómara Miren

机构信息

Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK.

NIHR Health Protection Research Unit in Gastrointestinal Infections at University of Liverpool, Liverpool, UK.

出版信息

medRxiv. 2025 Apr 4:2025.04.03.25324959. doi: 10.1101/2025.04.03.25324959.

Abstract

BACKGROUND

Infant rotavirus vaccination was introduced in the UK in July 2013, and was followed by a rapid reduction in rotavirus disease. We compare immunity to rotavirus in sera of age-stratified cohorts to assess the effect of vaccination on natural exposure to rotavirus.

METHODS

Residual serum samples were selected from a reference laboratory biobank based on age, and year of collection. Anti-rotavirus Immunoglobulin G (IgG) and IgA antibodies were measured using ELISA. We used censored linear spline regression models and anti-rotavirus IgA correlate of protection (CoP) thresholds to estimate immunity by age and vaccine eligibility (defined by date of birth).

RESULTS

We analysed serum from 1,200 individuals obtained between 2000 and 2019, of which 807 were vaccine-ineligible and 393 were vaccine-eligible. Among infants aged 3-11 months, a seven-fold increase in IgG levels was observed in the vaccine-eligible cohort (Geometric Mean Concentration [GMC], 1388.67 U/mL; 95% confidence interval [CI], 675.03-2856.78) compared to the vaccine-ineligible cohort (GMC, 198.54 U/ml; 95% CI, 71.31-552.78). Models showed increasing IgG and IgA antibody concentrations in the vaccine-ineligible cohort through childhood and into adulthood, but not in the vaccine-eligible cohort. The proportion of children <7 years with IgA≥160 U/ml, a proxy CoP against rotavirus disease, was lower among the vaccine-eligible population (adjusted odds ratio, 0.66; 95% CI, 0.48-0.91).

CONCLUSIONS

The introduction of rotavirus vaccination has reduced rotavirus disease burden but has disrupted the subsequent acquisition of naturally-acquired immunity. The impact of this on susceptibility to rotavirus disease in later life remains to be determined.

摘要

背景

2013年7月英国引入了婴儿轮状病毒疫苗,随后轮状病毒疾病迅速减少。我们比较了年龄分层队列血清中对轮状病毒的免疫力,以评估疫苗接种对轮状病毒自然暴露的影响。

方法

根据年龄和采集年份从参考实验室生物样本库中选择残留血清样本。使用酶联免疫吸附测定法测量抗轮状病毒免疫球蛋白G(IgG)和IgA抗体。我们使用删失线性样条回归模型和抗轮状病毒IgA保护相关性(CoP)阈值,按年龄和疫苗接种资格(由出生日期定义)估计免疫力。

结果

我们分析了2000年至2019年期间获得的1200人的血清,其中807人不符合疫苗接种条件,393人符合疫苗接种条件。在3至11个月大的婴儿中,符合疫苗接种条件的队列中IgG水平增加了7倍(几何平均浓度[GMC],1388.67 U/mL;95%置信区间[CI],675.03 - 2856.78),而不符合疫苗接种条件的队列中GMC为198.54 U/ml(95%CI,71.31 - 552.78)。模型显示,在不符合疫苗接种条件的队列中,儿童期至成年期IgG和IgA抗体浓度不断增加,但在符合疫苗接种条件的队列中并非如此。在符合疫苗接种条件的人群中,IgA≥160 U/ml(轮状病毒疾病的替代CoP)的7岁以下儿童比例较低(调整比值比,0.66;95%CI,0.48 - 0.91)。

结论

轮状病毒疫苗的引入减轻了轮状病毒疾病负担,但扰乱了随后自然获得性免疫的获得。这对晚年感染轮状病毒疾病易感性的影响仍有待确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/498e/11998831/f6233a5aa3f4/nihpp-2025.04.03.25324959v1-f0001.jpg

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