Potential risk of repeated nasal vaccination that induces allergic reaction with mucosal IgE and airway eosinophilic infiltration in cynomolgus macaques infected with H5N1 highly pathogenic avian influenza virus

The efficacy and detrimental effect of mucosal vaccination with an inactivated influenza vaccine were examined in a macaque model by intranasal administration with small amounts of inactivated whole virus particles and challenge by a human-derived H5N1 highly pathogenic avian influenza virus infection. Repeated nasal inoculation with the whole particle vaccine of an inactivated virus, A/duck/Hokkaido/Vac-3/2007 (H5N1) (Vac-3), induced antigen-specific IgA and IgG antibody production in nasal swabs and plasma. Vac-3-specific IgE production was also found in the nasal swabs. Nasal vaccination with Vac-3 induced broader cross-clade neutralization activity than did subcutaneous vaccination. After challenge infection, repeated nasal vaccination almost completely prevented the propagation of virus in the upper and lower airways and protected cynomolgus macaques from viral pneumonia by induction of IgA-producing B cells in the lungs. On the other hand, eosinophil clusters were observed in the lungs of vaccinated macaques. Although Vac-3-specific IgE antibody and IL-13 levels were decreased after infection compared to those before infection and no anaphylaxis in vaccinated macaques was detected after challenge infection, our results suggest that we have to pay attention to potential allergic responses at repeated nasal vaccination, especially in people who have an airway allergy.