Cross-protective immunity against influenza virus infections induced by intranasal vaccination together with a TLR3-mucosal adjuvant.

A new pandemic of influenza virus could result from the emergence of an unpredictable viral strain in an unexpected fashion. Thus, developing methods to protect the population from the spread of a new influenza virus is an urgent and important public health concern. Although vaccines can induce protective and prophylactic immune responses, the immunity induced by the current parenteral inactivated vaccine preparation is less effective in preventing heterologous virus infection. The induction of cross-protective mucosal immunity in the respiratory tract, the initial site of infection, is the most effective method for defending against heterologous influenza virus infection. Secretory immunoglobulin A plays a critical role in cross-protective mucosal immunity. Such cross-protective immunity can be induced by the intranasal administration of a vaccine together with an appropriate adjuvant that can mimic natural influenza virus infection. In this review, we describe the development of mucosal vaccines against influenza viruses and discuss their advantages. In addition, we describe data indicating that synthetic double-stranded RNAs, agonists of Toll-like receptor 3, are effective mucosal adjuvants for intranasally administered inactivated influenza virus vaccines.