Cross-protective and non-invasively administered
vaccines are attractive and highly desired for the control of
influenza. Self-assembling nanotechnology provides an opportunity for the development of
vaccines with superior performance. In this study, an intranasal
nanovaccine is developed targeting the conserved ectodomain of
influenza matrix protein 2(M2e). 3-sequential repeats of M2e (3M2e) is presented on the self-assembling recombinant human
heavy chain ferritin (rHF) cage to form the 3M2e-rHF nanoparticle. Intranasal vaccination with 3M2e-rHF nanoparticles in the absence of an adjuvant induces robust immune responses, including high titers of sera M2e-specific
IgG antibodies, T-cell immune responses, and mucosal
secretory-IgA antibodies in mice. The 3M2e-rHF nanoparticles also confer complete protection against a lethal
infection of homo-subtypic H1N1 and hetero-subtypic H9N2 virus. An analysis of the mechanism of protection underlying the intranasal immunization with the 3M2e-rHF nanoparticle indicates that M2e-specific mucosal
secretory-IgA and T-cell immune responses may play critical roles in the prevention of
infection. The results suggest that the 3M2e-rHF nanoparticle is a promising, needle-free, intranasally administered, cross-protective
influenza vaccine. The use of self-assembling
nanovaccines could be an ideal strategy for developing
vaccines with characteristics such as high immunogenicity, cross-protection, and convenient administration, as well as being economical and suitable for large-scale production.