Cumulative inactivated vaccine exposure and allergy development among children: A birth cohort from Japan

Kiwako Yamamoto-Hanada, Kyongsun Pak, Mayako Saito-Abe, Limin Yang, Miori Sato, Hidetoshi Mezawa, Hatoko Sasaki, Minaho Nishizato, Mizuho Konishi, Kazue Ishitsuka, Kenji Matsumoto, Hirohisa Saito, Yukihiro Ohya, Shin Yamazaki, Yukihiro Ohya, Reiko Kishi, Nobuo Yaegashi, Koichi Hashimoto, Chisato Mori, Shuichi ItoZentaro Yamagata, Hidekuni Inadera, Michihiro Kamijima, Takeo Nakayama, Hiroyasu Iso, Masayuki Shima, Youichi Kurozawa, Narufumi Suganuma, Koichi Kusuhara, Takahiko Katoh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Background: Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. Methods: We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children's Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. Results: Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028-1.893) or four to five 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; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; four or five vaccines vs. a single vaccine). Conclusions: Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. Trial registration: UMIN000030786.

Original languageEnglish
Article number27
JournalEnvironmental health and preventive medicine
Issue number1
Publication statusPublished - 2020 Jul 7


  • Adjuvant
  • Asthma
  • Eczema
  • Inactivated vaccine
  • Wheeze

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health


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