Associations of Initial Multiple Inactivated Vaccines with Later Allergies in JECS Children

Abstract

Background: Although we recognise that immunization is indispensable to global elimination of various diseases, the adjuvants used in inactivated vaccines often upregulate type 2 immunity that is dominant in allergic diseases. On the other hand, BCG vaccine is known to induce type 1 immunity. We hypothesised that administration during infancy of a greater number of vaccines that contain adjuvants may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. Methods: We obtained information regarding vaccinations and allergic diseases by using questionnaires that were used in The Japan Environment and Children's Study (JECS), i.e., a nationwide, multicentre, prospective birth cohort study including 103,099 pregnant women and their children. We examined for associations between the history of vaccination before 6 months of age and symptoms related to allergies at 12 months of age. Findings: Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving 3 (aOR 1.395, 95% CI 1.028-1.893) or 4-5 different inactivated vaccines (aOR 1.544, 95% CI 1.149-2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e., wheeze (aOR 1.238, 95% CI 1.094-1.401; 3 vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; 4 or 5 vaccines vs. a single vaccine). Interpretation: The prevalence of asthma, wheeze and eczema among children at 12 months of age was associated with having received a greater number of initial inactivated vaccines before 6 months of age. Although these results should be cautiously interpreted, we can at least postulate that development of better vaccines is needed to reduce the risk of later development of allergic diseases. Nevertheless, further studies should be conducted, and we are planning to extend the evaluation period until at least 13 years of age. Funding Statement: This study was funded and supported by the Ministry of the Environment, Japan. Declaration of Interests: All authors have no conflicts of interest related to this study. Ethics Approval Statement: The JECS protocol was reviewed and approved by the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies and by the ethics committees of all participating institutions. Written informed consent was obtained from all participants (i.e. pregnant women or other caregivers). The JECS was conducted in accordance with the Helsinki Declaration and other nationally valid regulations and guidelines.