Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses

Abstract

Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.

Immunomodulatory Nanosystems

“…[21,[244][245][246][247][248] In the prevention of these diseases, anti-infective vaccines used specific antigenic components instead of whole microbes in order to increase immune efficiency. [21,[244][245][246][247][248] In the prevention of these diseases, anti-infective vaccines used specific antigenic components instead of whole microbes in order to increase immune efficiency.…”

“…Sci. [247] The nanoparticle core showed strong immunogenicity and the coating layer mimicked the size and surface antigens of influenza virus. In one study, the trimeric form of HMG (3HMG) from H7N9 virus was assembled into nanoclusters before being cross-linked with an extra 3HMG layer on the surface.…”

Advancements in prophylactic and therapeutic nanovaccines

“…Sera from Uni4C13 immunized mice prevented the mice from a viral infection, indicating the role of serum antibodies. Also, antibodies specific to human M2e, PR8, and Aic were viable for four months after the immunization in mice and implied long-lasting protection [155] .…”

Nano-based approach to combat emerging viral (NIPAH virus) infection

“…The protein vaccine could induce substantial and prolonged immunity with complete protection of BALB/c mice against verity influenza A virus challenges. 104 With the contemporary improvement made in nanoscience it is certain that these impeccable polymeric NPs in near future will be soon used for the development of a novel antiviral against divergent array of infectious viruses like NiV.…”