Genetic predisposition to adverse events in Chinese children aged 3-24 months after diphtheria, tetanus, acellular pertussis and haemophilus influenzae type b combined vaccination

ABSTRACT

Background

Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs.

Methods

From July 2019 to June 2020, we performed a case-control study among children aged 3–24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs.

Results

304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44–36.58, P = 0.0165).

Conclusion

Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.

KEYWORDS:

• Genetic predisposition
• children
• adverse effects
• DTaP-Hib

Acknowledgments

We thank Hangzhou Municipal Center for Disease Control and Prevention, Yinzhou District Center for Disease Control and Prevention, Qianjiang Municipal Center for Disease Control and Prevention, Ziyang Municipal Center for Disease Control and Prevention, Chaoyang District Center for Disease Control and Prevention, Tongzhou District Center for Disease Control and Prevention, Taocheng District Center for Disease Control and Prevention for invaluable assistance in study setup and sample collection.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Dafang Chen conceived the study, undertook project leadership and he was also the guarantor of this work. Yujia Ma wrote the first draft of the manuscript, analyzed data and interpreted the results. Yexiang Sun, Peng Shen, Yuyang Xu, Chunyan Zhao, Changfei Liu were involved in the data collection. Zechen Zhou, Xiaoyi Li, Zeyu Yan, Kexin Ding and Han Xiao supervised the analyses and methodology. All authors contributed to the drafting and critical revision of the manuscript. All authors read and approved the final version of the manuscript.

Data availability statement

PLINK (https://zzz.bwh.harvard.edu/plink/) was used to estimate the odds ratio (OR), z value, and P-value and haplotype association analysis. Haploview (https://www.broadinstitute.org/haploview/haploview) was used to create haplotypes and estimate pairwise linkage disequilibrium (LD) using the r-squared statistic.

Ethical approval and consent to participate

This study was approved by the Ethics Committee of the Peking University Health Science Center (Approval number: IRB00001052-19,022), and written informed consent was provided by all participants.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2022.2144239

Additional information

Funding

This paper was funded by Beijing Natural Science Foundation (No.L192054).