Intranasal Nanovaccine Confers Homo‐ and Hetero‐Subtypic Influenza Protection

Abstract 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.