Objectives: To identify the cause of the anaphylaxis events in 2011-12 in Japan.
Methods: We collected serum and blood specimens of IVA cases within 2 months after the events from all areas of Japan. The diagnosis was confirmed based on the Brighton collaboration case definition of anaphylaxis of level 1 and 2. Eighteen cases of confirmed IVA and age-matched 7 control subjects with the similar vaccination history were examined. Specific IgE to each component, namely A/H1, A/H3 and B, of the trivalent vaccines distributed for 2011-12 season from several vaccine manufacturers was measured with ELISA. Antigen-induced basophil activation was evaluated by measurement of CD203c expression with flowcytometry. Effects of additives to the vaccine preparations on the CD203c expression were also examined.
Results: No patients with IVA had egg allergy. Specific-IgE antibodies to A/H1, A/H3 and B were significantly elevated in patients with IVA than in controls. No differences in IgE antibody titers among components or products from different manufacturers were identified. Influenza vaccine component-induced CD203c expression in basophils were also highly enhanced in IVA and no response was observed in controls. Since the IVA cases segregated in patients who received phenoxyethanol-containing vaccines, effect of the preservative on basophil activation was examined and enhancement with phenoxyethanol, not with thimerosal, of the response was observed in some cases.
Conclusions:
The results suggest that the recent IVA in Japan was caused by specific IgE antibodies to influenza vaccine components and that phenoxyethanol may have modified the reaction. Measurement of vaccine-component –specific IgE and basophil activation is useful for diagnosis of vaccine-associated anaphylaxis.