Fc receptor is not required for inducing antibodies but plays a critical role in conferring protection after influenza M 2 vaccination

Summary The ectodomain of matrix protein 2 ( M 2e) of influenza virus is considered a rational target for a universal influenza A vaccine. To better understand M 2e immune‐mediated protection, F c receptor common γ chain deficient ( F c R γ −/− ) and wild‐type mice were immunized with a tandem repeat of M 2e presented on virus‐like particles ( M 2e5x VLP ). Levels of M 2e‐specific antibodies that were induced in F c R γ −/− mice after immunization with M 2e5x VLP were similar to those in wild‐type mice. In addition, M 2e antibodies induced in F c R γ −/− mice were found to be equally protective as those induced in wild‐type mice. However, M 2e5x VLP ‐immunized F c R γ −/− mice were not well protected, as shown by severe weight loss, higher lung viral titres and interleukin‐6 inflammatory cytokine production upon influenza virus challenge compared with M 2e5x VLP ‐immunized wild‐type mice. Importantly, F c R γ −/− mice that were immunized with inactivated influenza virus induced haemagglutination inhibition activity and were well protected without a significant weight loss. Interestingly, interferon‐ γ ‐producing CD 4 T and CD 8 T cells were found to be prevalent in lungs from M 2e5x VLP ‐immunized F c R γ −/− mice, which appeared to be correlated with a faster recovery after infection. These results indicate that F c receptors play a primary role in conferring M 2e‐specific antibody‐mediated protection whereas T cells may contribute to the recovery at later stages of infection.