Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice

Abstract

Influenza is a persistent threat to public health. Here we report that double-layered peptide nanoparticles induced robust specific immunity and protected mice against heterosubtypic influenza A virus challenges. We fabricated the nanoparticles by desolvating a composite peptide of tandem copies of nucleoprotein epitopes into nanoparticles as cores and cross-linking another composite peptide of four tandem copies of influenza matrix protein 2 ectodomain epitopes to the core surfaces as a coating. Delivering the nanoparticles via dissolvable microneedle patch-based skin vaccination further enhanced the induced immunity. These peptide-only, layered nanoparticles demonstrated a strong antigen depot effect and migrated into spleens and draining (inguinal) lymph nodes for an extended period compared with soluble antigens. This increased antigen-presentation time correlated with the stronger immune responses in the nanoparticle-immunized group. The protection conferred by nanoparticle immunization was transferable by passive immune serum transfusion and depended partially on a functional IgG receptor FcγRIV. Using a conditional cell depletion, we found that CD8 T cells were involved in the protection. The immunological potency and stability of the layered peptide nanoparticles indicate applications for other peptide-based vaccines and peptide drug delivery.

Microneedle‐based intradermal delivery of stabilized dengue virus

“…Coated and dissolvable MNs represent dry formulations, which compared to liquid-based injectable vaccines are easier to store, require lesser space and weight capacity for storage, and have reduced cost of transport. Such designs have been developed for viruses including influenza, 22,[26][27][28][29][30][31][32][33][34][35][36][37] hepatitis B, [38][39][40][41] hepatitis C, 42 polio, 43,44 herpes simplex, 45,46 human papillomavirus, 47,48 rotavirus, 49 measles and rubella, 50-52 rabies, 53 HIV, 54,55 Ebola, 56 chikungunya, and West Nile virus. 57 However despite extensive advances in MN-based vaccines, there are limited studies addressing the delivery of LAVs.…”

Materials for Immunotherapy

“…As alternatives to CMC, chitosan in combination with PLA and sucrose in combination with threonine as well as PVA have been used to make fully dissolvable microneedles. Recently, Wang and Prausnitz developed a dissolvable microneedle made from PVA and sucrose to deliver peptide nanoparticles as a vaccine against H1N1 influenza . One notable challenge with most polysaccharide microneedles is their weak mechanical properties (e.g., softness and sometimes brittleness).…”

Influenza Vaccines toward Universality through Nanoplatforms and Given by Microneedle Patches

“…Some conserved HLA I and II-recognized epitopes have been characterized. Fusion peptides and recombinant proteins including these epitopes have been studied in laboratory animals and showed strong T cell responses and broad protection [ 42 , 43 , 44 , 45 ]. However, novel approaches are to be investigated to identify and utilize new NP T cell epitopes to design novel immunogens for a universal influenza vaccine.…”