University of Oulu

Gao, Y-d, Xepapadaki, P, Cui, Y-w, et al. Effect of Haemophilus influenzae, Streptococcus pneumoniae and influenza vaccinations on infections, immune response and asthma control in preschool children with asthma. Allergy. 2023; 78: 1473-1488. doi: 10.1111/all.15551

Effect of Haemophilus influenzae, Streptococcus pneumoniae and influenza vaccinations on infections, immune response and asthma control in preschool children with asthma

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Author: Gao, Ya-dong1,2; Xepapadaki, Paraskevi3; Cui, Yan-wen1;
Organizations: 1Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, China
2Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
3Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
4Swiss Research Institute for Sports Medicine (SRISM), Davos, Switzerland
5Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
6Upper Airway Research Laboratory, Ghent University Hospital, Ghent, Belgium
7Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
8Department of Immunology and Allergy, Medical University of Lodz, Lodz, Poland
9Department of Pediatrics, Oulu University Hospital, Oulu, Finland
10PEDEGO Research Unit, University of Oulu, Oulu, Finland
11Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
12School of Public Health, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
13Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK
Format: article
Version: accepted version
Access: embargoed
Persistent link:
Language: English
Published: John Wiley & Sons, 2023
Publish Date: 2024-05-31


Background: Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (pneumococcus) and influenza vaccines are administered in children to prevent infections caused by these pathogens. The benefits of vaccination for asthma control in children and the elicited immune response are not fully understood. This study aimed to investigate the impact of these vaccinations on respiratory infections, asthma symptoms, asthma severity and control status, pathogen colonization and in vitro immune responses to different stimulants mimicking infections in asthmatic children.

Methods: Children aged 4–6 years were recruited into the multicentre prospective PreDicta study conducted across five European countries. Information about vaccination history, infections, antibiotic use, inhaled corticosteroid (ICS) use and asthma symptoms in the last 12 months were obtained from questionnaires of the study. Nasopharyngeal samples were collected at the first visit to assess bacterial and viral colonization, and venous blood for isolation of peripheral blood mononuclear cells (PBMCs). The PBMCs were stimulated with phytohemagglutinin, R848, Poly I:C and zymosan. The levels of 22 cytokines and chemokines were measured in cell culture supernatants using a luminometric multiplex assay.

Results: One-hundred and forty asthmatic preschool children (5.3 ± 0.7 years) and 53 healthy children (5.0 ± 0.8 years) from the PreDicta cohort were included in the current study. Asthmatic children were associated with more frequent upper and lower respiratory infections, and more frequent and longer duration of antibiotic use compared with healthy children. In asthmatic children, sufficient H. influenzae vaccination was associated with a shorter duration of upper respiratory infection (URI) and overall use and average dose of ICS. The airway colonization was characterized by less pneumococcus and more rhinovirus. Pneumococcal vaccination was associated with a reduction in the use rate and average dose of ICS, improved asthma control, and less human enterovirus and more H. influenzae and rhinovirus (RV) airway colonization. Influenza vaccination in the last 12 months was associated with a longer duration of URI, but with a decrease in the occurrence of lower respiratory infection (LRI) and the duration of gastrointestinal (GI) infection and antibiotic use. Asthmatic preschoolers vaccinated with H. influenzae, pneumococcus or influenza presented higher levels of Th1-, Th2-, Th17- and regulatory T cells (Treg)-related cytokines in unstimulated PBMCs. Under stimulation, PBMCs from asthmatic preschoolers with pneumococcal vaccination displayed a predominant anti-inflammatory immune response, whereas PBMCs from asthmatic children with sufficient H. influenzae or influenza vaccination were associated with both pro- and anti-inflammatory immune responses.

Conclusion: In asthmatic preschoolers, the standard childhood vaccinations to common respiratory pathogens have beneficial effects on asthma control and may modulate immune responses relevant to asthma pathogenesis.

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Series: Allergy
ISSN: 0105-4538
ISSN-E: 1398-9995
ISSN-L: 0105-4538
Volume: 78
Issue: 6
Pages: 1473 - 1488
DOI: 10.1111/all.15551
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3123 Gynaecology and paediatrics
Funding: This study was funded by PreDicta, EU 7th framework program, Contract No: HEALTH-f2-2010-260895 and the Swiss National Science Foundation.
Copyright information: © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Gao, Y-d, Xepapadaki, P, Cui, Y-w, et al. Effect of Haemophilus influenzae, Streptococcus pneumoniae and influenza vaccinations on infections, immune response and asthma control in preschool children with asthma. Allergy. 2023; 78: 1473-1488, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.