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BMC Medicine
Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Coxsackievirus | Research article

The transfer of maternal antibodies and dynamics of maternal and natural infection-induced antibodies against coxsackievirus A16 in Chinese children 0–13 years of age: a longitudinal cohort study

Authors: Jiaxin Zhou, Yonghong Zhou, Kaiwei Luo, Qiaohong Liao, Wen Zheng, Hui Gong, Huilin Shi, Shanlu Zhao, Kai Wang, Qi Qiu, Bingbing Dai, Lingshuang Ren, Lili Wang, Lidong Gao, Meng Xu, Nuolan Liu, Wanying Lu, Nan Zheng, Xinhua Chen, Zhiyuan Chen, Juan Yang, Simon Cauchemez, Hongjie Yu

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

A major hand-foot-and-mouth disease (HFMD) pathogen, coxsackievirus A16 (CVA16), has predominated in several of the last 10 years and caused the largest number of HFMD outbreaks between 2011 and 2018 in China. We evaluated the efficacy of maternal anti-CVA16 antibody transfer via the placenta and explored the dynamics of maternal and natural infection-induced neutralizing antibodies in children.

Methods

Two population-based longitudinal cohorts in southern China were studied during 2013–2018. Participants were enrolled in autumn 2013, including 2475 children aged 1–9 years old and 1066 mother-neonate pairs, and followed for 3 years. Blood/cord samples were collected for CVA16-neutralizing antibody detection. The maternal antibody transfer efficacy, age-specific seroprevalence, geometric mean titre (GMT) and immune response kinetics were estimated.

Results

The average maternal antibody transfer ratio was 0.88 (95% CI 0.80–0.96). Transferred maternal antibody levels declined rapidly (half-life: 2.0 months, 95% CI 1.9–2.2 months). The GMT decayed below the positive threshold (8) by 1.5 months of age. Due to natural infections, it increased above 8 after 1.4 years and reached 32 by 5 years of age, thereafter dropping slightly. Although the average duration of maternal antibody-mediated protection was < 3 months, the duration extended to 6 months on average for mothers with titres ≥ 64.

Conclusions

Anti-CVA16 maternal antibodies are efficiently transferred to neonates, but their levels decline quickly. Children aged 0–5 years are the main susceptible population and should be protected by CVA16 vaccination, with the optimal vaccination time between 1.5 months and 1 year of age.
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Literature
1.
Tapparel C, Siegrist F, Petty TJ, Kaiser L. Picornavirus and enterovirus diversity with associated human diseases. Infect Genet Evol. 2013;14:282–93.CrossRefPubMed
2.
Zhang Z, Liu Y, Liu F, Ren M, Nie T, Cui J, et al. Basic Reproduction Number of Enterovirus 71 and Coxsackievirus A16 and A6: Evidence From Outbreaks of Hand, Foot, and Mouth Disease in China Between 2011 and 2018. Clin Infect Dis. 2021;73(9):e2552–9.CrossRefPubMed
3.
Mao Q, Wang Y, Yao X, Bian L, Wu X, Xu M, et al. Coxsackievirus A16: epidemiology, diagnosis, and vaccine. Hum Vaccin Immunother. 2014;10(2):360–7.CrossRefPubMed
4.
Xu W, Liu CF, Yan L, Li JJ, Wang LJ, Qi Y, et al. Distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications. Virol J. 2012;9:8.CrossRefPubMedPubMedCentral
5.
Li R, Liu L, Mo Z, Wang X, Xia J, Liang Z, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med. 2014;370(9):829–37.CrossRefPubMed
6.
Zhu F, Xu W, Xia J, Liang Z, Liu Y, Zhang X, et al. Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China. N Engl J Med. 2014;370(9):818–28.CrossRefPubMed
7.
Zhu F-C, Meng F-Y, Li J-X, Li X-L, Mao Q-Y, Tao H, et al. Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2013;381(9882):2024–32.CrossRefPubMed
8.
9.
Cáceres VM, Strebel PM, Sutter RW. Factors Determining Prevalence of Maternal Antibody to Measles Virus throughout Infancy: A Review. Clin Infect Dis. 2000;31(1):110–9.CrossRefPubMed
10.
Hong J, Li L, Liu YM, Ge HM, Wang XS, Hu JL, et al. Seroepidemiology of human enterovirus71 and coxsackievirusA16 in Jiangsu province, China. Virol J. 2012;9:248.
11.
Fu C, Lu L, Wu H, Shaman J, Cao Y, Fang F, et al. Placental antibody transfer efficiency and maternal levels: specific for measles, coxsackievirus A16, enterovirus 71, poliomyelitis I-III and HIV-1 antibodies. Sci Rep. 2016;6:38874.CrossRefPubMedPubMedCentral
12.
Cui M, Ya-Jing LI, Yang QY, Long LU, Qing HE, Dong ZQ, et al. Study on transition levels of maternal neutralizing antibodies against enterovirus 71 and coxsackievirus A16 in infants in Guangzhou. Chin J Dis Control Prev. 2016;20(3):236–9.
13.
Wei XIA, Yan LI, Yin DP, et al. Investigatioin on Neutralizing Antibody Level of Enterovirus Type 71 and Coxsackievirus Group Type 16 among Mothers and Newborns in Six Counties. Chin J Vacc Immun. 2013;19(02):164–167+174.
14.
Mao Q-y, Liao XY, Yu X, Li N, Zhu F-c, Zeng Y, et al. Dynamic change of mother-source neutralizing antibodies against enterovirus 71 and coxsackievirus A16 in infants. Chin Med J (Engl). 2010;123(13):1679–84.
15.
Zhu FC, Liang ZL, Meng FY, Zeng Y, Mao QY, Chu K, et al. Retrospective study of the incidence of HFMD and seroepidemiology of antibodies against EV71 and CoxA16 in prenatal women and their infants. PLoS One. 2012;7(5):e37206.CrossRefPubMedPubMedCentral
16.
Kim S, Bae KS, Kim JH, Kang JH, Choi UY. Seroprevalence of Neutralizing Antibodies Against Candidate Serotypes of Enterovirus Vaccines Among Korean Children. Viral Immunol. 2021;34(2):62–7.CrossRefPubMed
17.
Wei AL, Joanne T, Chee PM, Pu HJ, Jeffery C, Lyn J, et al. Seroepidemiology of Coxsackievirus A6, Coxsackievirus A16, and Enterovirus 71 Infections among Children and Adolescents in Singapore, 2008-2010. PLoS One. 2015;10(5):e0127999.CrossRef
18.
Hatairat L, Jarunee P, Anek M, Chompunuch K, Pirom, Journal NJV. Seroprevalence of antibodies to enterovirus 71 and coxsackievirus A16 among people of various age groups in a northeast province of Thailand. Virol J. 2018;15(1):158.CrossRef
19.
Rabenau HF, Richter M, Doerr HW. Hand, foot and mouth disease: seroprevalence of Coxsackie A16 and Enterovirus 71 in Germany. Med Microbiol Immunol. 2010;199(1):45–51.CrossRefPubMed
20.
Ni H, Yi B, Yin J, Fang T, He T, Du Y, et al. Epidemiological and etiological characteristics of hand, foot, and mouth disease in Ningbo, China, 2008–2011. J Clin Virol. 2012;54(4):342–8.CrossRefPubMed
21.
Wei X, Yang J, Gao L, Wang L, Liao Q, Qiu Q, et al. The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother-neonate cohort study. Lancet Infect Dis. 2021;21(3):418–26.CrossRefPubMed
22.
Gao L, Zou G, Liao Q, Zhou Y, Liu F, Dai B, et al. Spectrum of Enterovirus Serotypes Causing Uncomplicated Hand, Foot, and Mouth Disease and Enteroviral Diagnostic Yield of Different Clinical Samples. Clin Infect Dis. 2018;67(11):1729–35.CrossRefPubMed
23.
Xing W, Liao Q, Viboud C, Zhang J, Sun J, Wu JT, et al. Hand, foot, and mouth disease in China, 2008–12: an epidemiological study. Lancet Infect Dis. 2014;14(4):308–18.CrossRefPubMedPubMedCentral
24.
Qiu Q, Zhou J, Cheng Y, Zhou Y, Liang L, Cui P, et al. Kinetics of the neutralising antibody response in patients with hand, foot, and mouth disease caused by EV-A71: a longitudinal cohort study in Zhengzhou during 2017-2019. EBioMedicine. 2021;68:103398.CrossRefPubMedPubMedCentral
25.
Dang S, Gao N, Li Y, Li M, Wang X, Jia X, et al. Dominant CD4-dependent RNA-dependent RNA polymerase-specific T-cell responses in children acutely infected with human enterovirus 71 and healthy adult controls. Immunology. 2014;142(1):89–100.CrossRefPubMedPubMedCentral
26.
Hartter HK, Oyedele OI, Dietz K, Kreis S, Hoffman JP, Muller CP. Placental transfer and decay of maternally acquired antimeasles antibodies in Nigerian children. Pediatr Infect Dis J. 2000;19(7):635–41.CrossRefPubMed
27.
Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 2007;7(9):715–25.CrossRefPubMed
28.
Fu C, Shen J, Lu L, Li Y, Cao Y, Wang M, et al. Pre-vaccination evolution of antibodies among infants 0, 3 and 6months of age: A longitudinal analysis of measles, enterovirus 71 and coxsackievirus 16. Vaccine. 2017;35(31):3817–22.CrossRefPubMedPubMedCentral
29.
Mao QY, Liao XY, Xiang YU, Nan LI, Zhu FC, Zeng Y, et al. Dynamic change of mother-source neutralizing antibodies against enterovirus 71 and coxsackievirus A16 in infants. Chin Med J (Engl). 2010;123(13):1679–84.
30.
D S. Serological survey of hand, foot and mouth disease among healthy people in Hebei District, Tianjin City, 2016 ~ 2019 Year. Med Inform. 2020;33(8):147–9.
31.
Gao F, Mao QY, Chen P, Bian LL, Yao X, Li JX, et al. Seroepidemiology of Coxsackievirus A6, Coxsackievirus A16, and Enterovirus 71 infections in infants and children: A prospective cohort study in Jiangsu, China. J Infect. 2016;73(5):509–12.CrossRefPubMed
32.
Yu N, Guo M, He SJ, Pan YX, Chen XX, Ding XX, et al. Evaluation of human enterovirus 71 and coxsackievirus A16 specific immunoglobulin M antibodies for diagnosis of hand-foot-and-mouth disease. Virol J. 2012;9:12.CrossRefPubMedPubMedCentral
33.
Nguyet LA, Thanh TT, Nhan LNT, Hong NTT, Nhu LNT, Van HMT, et al. Neutralizing Antibodies against Enteroviruses in Patients with Hand, Foot and Mouth Disease. Emerg Infect Dis. 2020;26(2):298–306.CrossRefPubMedPubMedCentral
34.
Ren J, Wang X, Zhu L, Hu Z, Gao Q, Yang P, et al. Structures of Coxsackievirus A16 Capsids with Native Antigenicity: Implications for Particle Expansion, Receptor Binding, and Immunogenicity. J Virol. 2015;89(20):10500–11.CrossRefPubMedPubMedCentral
35.
Lim C, Jiang L, Ma S, James L, Ang LWJE. Infection: Basic reproduction number of coxsackievirus type A6 and A16 and enterovirus 71: estimates from outbreaks of hand, foot and mouth disease in Singapore, a tropical city-state. Epidemiol Infect. 2016;144(05):1028–34.CrossRefPubMed
36.
Ma E, Fung C, Yip S, Wong C, Chuang SK. Tsang TJTPIDJ: Estimation of the basic reproduction number of enterovirus 71 and coxsackievirus A16 in hand, foot, and mouth disease outbreaks. Pediatr Infect Dis J. 2011;30(8):675–9.CrossRefPubMed
37.
Takahashi S, Liao Q, Van Boeckel TP, Xing W, Sun J, Hsiao VY, et al. Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination. PLoS Med. 2016;13(2):e1001958.CrossRefPubMedPubMedCentral
38.
Mazzilli S, Tavoschi L, Lopalco PL. Tdap vaccination during pregnancy to protect newborns from pertussis infection. Annali Igiene : Med Prev Comunita. 2018;30(4):346–63.
39.
Trostle ME, Aguero-Rosenfeld ME, Roman AS, Lighter JL. High antibody levels in cord blood from pregnant women vaccinated against COVID-19. Am J Obstet Gynecol MFM. 2021;3(6):100481.CrossRefPubMedPubMedCentral
40.
Hoang CQ, Nguyen HD, Ho NX, Vu THT, Pham TTM, Nguyen KT, et al. Incidence of Infection of Enterovirus 71 and Coxsackieviruses A6 and A16 among Household Contacts of Index Cases in Dong Thap Province, Southern Vietnam. BioMed Res Int. 2020;2020:9850351.CrossRefPubMedPubMedCentral
41.
Wang JX, Zhu SL, Jing W, Lin Y, Pei YW, Sun DP, et al. Ding SJJPO: Seroprevalence of Enterovirus A71 and Coxsackievirus A16 in Healthy People in Shandong Province, China. PLoS One. 2016;11(9):e0162373.CrossRefPubMedPubMedCentral
42.
Wang X, Xing M, Zhang C, Yang Y, Chi Y, Tang X, et al. Neutralizing antibody responses to enterovirus and adenovirus in healthy adults in China. Emerg Microbes Infect. 2014;3(5):e30.PubMedPubMedCentral
Metadata
Title
The transfer of maternal antibodies and dynamics of maternal and natural infection-induced antibodies against coxsackievirus A16 in Chinese children 0–13 years of age: a longitudinal cohort study
Authors
Jiaxin Zhou
Yonghong Zhou
Kaiwei Luo
Qiaohong Liao
Wen Zheng
Hui Gong
Huilin Shi
Shanlu Zhao
Kai Wang
Qi Qiu
Bingbing Dai
Lingshuang Ren
Lili Wang
Lidong Gao
Meng Xu
Nuolan Liu
Wanying Lu
Nan Zheng
Xinhua Chen
Zhiyuan Chen
Juan Yang
Simon Cauchemez
Hongjie Yu
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02604-w

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