ARTICLES| VOLUME 4, ISSUE 11, E893-E902, NOVEMBER 2023Download Full Issue

Transplacental transfer efficiency of maternal antibodies against influenza A(H1N1)pdm09 virus and dynamics of naturally acquired antibodies in Chinese children: a longitudinal, paired mother–neonate cohort study

Mei Li, Wei Wang, Junbo Chen, et al

Lancet Microbe 2023; 4: E893-E902 Published:October 09, 2023 DOI:https://doi.org/10.1016/S2666-5247(23)00181-7

Summary

Background

The 2009 pandemic H1N1 influenza A virus (A(H1N1)pdm09 virus) evolves rapidly and has continued to cause severe infections in children since its emergence in 2009. We aimed to characterise the kinetics of maternally and naturally acquired antibodies against historical A(H1N1)pdm09 strains and to assess the extent to which the response to heterologous strains following infection or vaccination affects observed A(H1N1)pdm09 strain-specific antibody titres in a Chinese paediatric population.

背景 2009 年新型甲型 H1N1 流感病毒出现以来，其抗原变异频繁，持续引起儿童的严重感
染。本研究旨在描述甲型 H1N1 流感病毒的母传和自然感染诱导抗体的动力学特征，并评估
自然感染或疫苗接种对甲型 H1N1 流感病毒毒株特异性抗体滴度的影响。

Methods

In this retrospective study, we used residual serum samples from 528 mother-neonate pairs from a non-interventional, longitudinal cohort study in southern China conducted from Sept 20, 2013, to Aug 24, 2018, from six local hospitals in Anhua County, Hunan Province, China. Mother-neonate pairs were eligible for inclusion if the neonates were born after Sept 20, 2013, and their mothers had resided in the study sites for at least 3 months. We tested samples with a haemagglutination inhibition (HAI) assay to measure antibody levels against three historical A(H1N1)pdm09 strains that were antigenically similar to the strains that circulated during the 2009 pandemic (A/Hunan-Kaifu/SWL4204/2009 [SWL4204/09 strain], A/Hunan-Daxiang/SWL1277/2016 [SWL1277/16 strain], and A/Hunan-Yanfeng/SWL185/2018 [SWL185/18 strain]). We also determined the seroprevalence, geometric mean titres (GMTs), transfer ratio of maternal antibodies, and the dynamics of maternally and naturally acquired antibodies in children, from birth to 3 years of age.

方法 基于 2018 年 9 月 20 日至 8 月 24 日在中国湖南省安化县建立的非干预性纵向队列，
本研究选择了 528 名队列儿童及其母亲作为研究对象。 采用血凝抑制实验（haemagglutination
inhibition， HAI） ，本研究检测了上述研究对象剩余血清标本中的甲型 H1N1 流感病毒 A/Hunan-
Kaifu/SWL4204/2009（SWL4204/09）、A/Hunan-Daxiang/SWL1277/2016（SWL1277/16）以及
A/Hunan-Yanfeng/SWL185/2018（SWL185/18）毒株的 HAI 抗体水平。随后，研究确定了各毒
株的血清阳性率、抗体几何平均滴度（geometric mean titre，GMT）、母传抗体传输比以及儿
童自出生至 3 周岁期间的母传和自然感染诱导抗体的动态变化。

Findings

1066 mother-neonate pairs were enrolled in the original cohort between Sept 20, 2013, and Oct 14, 2015. Of these, 528 pairs (523 mothers, 528 neonates) were selected for the present study. The median age of the mothers was 25 years (IQR 23 to 29). 291 (55%) of 528 children were boys and 237 (45%) were girls, and most children (452 [86%]) were breastfed before the age of 6 months. The GMTs and the seroprevalence for the SWL4204/09 strain were higher than those for the SWL1277/16 and SWL185/18 strains among mothers (GMTs: 10·4 [95% CI 9·8 to 11·1] vs 9·3 [8·7 to 9·8] vs 8·0 [7·5 to 8·4], p<0·0001; seroprevalence: 11·1% [95% CI 8·5 to 14·1] vs6·9% [4·9 to 9·4] vs 4·6% [3·0 to 6·8], p=0·0003) and among neonates (GMTs: 10·7 [10·0 to 11·5] vs 9·4 [8·8 to 10·0] vs 8·1 [7·6 to 8·6], p<0·0001; seroprevalence: 13·4% [10·7 to 16·7] vs 8·7% [6·5 to 11·5] vs 6·1% [4·2 to 8·5], p=0·0002). Regardless of the A(H1N1)pdm09-specific strain, maternal antibodies could be transferred efficiently via the placenta (mean transfer ratios: 1·10 for SWL4204/09 vs1·09 for SWL1277/16 vs 1·06 for SWL185/18; p=0·93). The A(H1N1)pdm09 strain-specific antibodies waned below the protective threshold of 1:40 within 2 months after birth. After maternal antibody waning, there were periodic increases and decreases in HAI antibody titres against three A(H1N1)pdm09 strains, and such increases were all significantly associated with a higher immune response to heterologous strains. Vaccination against the SWL4204/09 strain was associated with a poor response to the SWL185/18 strain (β–0·20, 95% CI –0·28 to –0·13; p<0·0001).

结果 2013 年 9 月 20 日至 2015 年 10 月 14 日， 队列共纳入 1066 名儿童及其母亲，其中 528
对母婴对 （包括 523 名母亲和 528 名新生儿） 被纳入本研究。 在本研究中， 母亲的中位年龄
为 25 岁（IQR 23-29）；男孩为 291 名（55%），女孩为 237 名（45%）；452 名（86%）儿
童在 6 月龄前接受了母乳喂养。研究发现，母亲（GMT：10.4 [95% CI：9.8-11.1]，9.3 [8.7-
9.8]，8.0 [7.5-8.4]，p<0.0001；血清阳性率：11.1% [95% CI：8.5-14.1]，6.9% [4.9-9.4]，4.6%
[3.0-6.8]， p=0.0003）和新生儿（GMT： 10.7 [10.0-11.5]， 9.4 [8.8-10.0]， 8.1 [7.6-8.6]， p<0.0001；
血清阳性率：13.4% [10.7-16.7]，8.7% [6.5-11.5]，6.1% [4.2-8.5]，p=0.0002）的 SWL4204/09
株的 GMT 和血清阳性率均高于 SWL1277/16 和 SWL/185/18 株。不论何种毒株，母亲抗体均
可通过胎盘有效传输给新生儿 （平均传输比： SWL4204/09 株为 1.10、 SWL1277/16 株为 1.09、
SWL185/18 株为 1.06，p=0.93）。研究还发现，各毒株的 HAI 抗体在儿童出生后 2 个月内衰
减到保护阈值 1:40 以下；母传抗体衰减后，HAI 抗体滴度呈现周期性升高和下降，并且各
毒株的抗体滴度的周期性升高与异种毒株抗体滴度的升高显著相关；针对 SWL4204/09 株的
疫苗接种与 SWL185/18 株抗体滴度的降低有关（β=-0.20， 95%CI：-0.28 至-0.13， p＜0.0001）。

Interpretation

Our findings suggest low pre-existing immunity against influenza A(H1N1)pdm09 virus among unvaccinated Chinese adult female and paediatric populations. This evidence, together with the rapid decay of maternal antibodies and the observed cross-reactivity among different A(H1N1)pdm09 strains, highlights the importance of accelerating maternal and paediatric influenza vaccination in China.

解读 研究提示，未接种流感疫苗的中国成年女性和儿童针对甲型 H1N1 流感病毒的预存免
疫力较低。 此发现与母传抗体的快速衰减、 不同甲型 H1N1 流感病毒毒株间的交叉保护共同
强调了在中国加快母亲和儿童流感疫苗接种的重要性。

Funding

The Key Program of the National Natural Science Foundation of China.