Influenza A whole virion vaccine induces a rapid reduction of peripheral blood leukocytes via interferon-α-dependent apoptosis

Manabu Ato, Yoshimasa Takahashi, Hideki Fujii, Shu ichi Hashimoto, Tomohiro Kaji, Shigeyuki Itamura, Yoshinobu Horiuchi, Yoshichika Arakawa, Masato Tashiro, Toshitada Takemori

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Infection with single strand RNA (ssRNA) viruses, such as influenza A virus, is known to induce protective acquired immune responses, including the production of neutralizing antibodies. Vaccination also causes a reduction in the number of peripheral blood leukocytes (PBL) shortly after inoculation, a result which may have undesirable adverse effects. The cellular mechanisms for this response have not been elucidated so far. Here we report that formalin-inactivated influenza A whole virus vaccine (whole virion) induces a significant decrease in PBL in mice 5-16. h after administration, whereas an ether-split vaccine (HA split) made from the same influenza virus strain does not induce a similar loss of PBL. Concordant with this reduction in the number of PBL, a rapidly induced and massive production of interferon (IFN)-α is observed when mice are injected with whole virion, but not with HA split vaccines. The role of Toll-like receptors (TLR), which are involved in signal transduction of influenza virus, and the subsequent induction of IFNα were confirmed using mice lacking TLR7, MyD-88, or IFNα/β receptor. We further demonstrated that the observed PBL loss is caused by apoptosis in an IFNα-dependent manner, and not by leukocyte redistribution due to chemokine signaling failure. These findings indicate that RNA-encapsulated whole virion vaccines can rapidly induce a loss of leukocytes from peripheral blood by apoptosis, which may modulate the subsequent immune response.

Original languageEnglish
Pages (from-to)2184-2190
Number of pages7
JournalVaccine
Volume31
Issue number17
DOIs
Publication statusPublished - 2013 Apr 19

Keywords

  • Apoptosis
  • Inactivated influenza vaccine
  • Innate immunity
  • Leukocytopenia
  • Type-I interferons

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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