M2e-Derived Peptidyl and Peptide Amphiphile Micelles as Novel Influenza Vaccines

Abstract

A significant problem with current influenza vaccines is their reliance on predictions of what will be the most prevalent strains for the upcoming season. Mismatches between predictions and reality in any given year can greatly reduce the overall efficacy of an immunization campaign. A universal influenza vaccine, which leverages epitopes conserved across many, if not all, strains of influenza, can reduce the need for such accurate forecasting. The ectodomain of the M2 ion channel protein is highly conserved and includes a B cell epitope in the M2_2-16 region, making it a potentially viable candidate as a universal influenza vaccine. Unfortunately, the use of free peptide antigens as vaccines comes with several disadvantages including poor stability and weak immunogenicity in vivo. However, integrating peptide antigens into nanoparticles can avoid some of those drawbacks. Previous studies have shown that micellar nanoparticles can be generated from peptides by conjugating them with a lipid or lipids. Specifically, hydrophobically-driven, self-assembled peptide amphiphile micelles comprised of Palm₂K-peptide-(KE)₄ have been found to be immunostimulatory. Unlike other peptides previously used for this purpose, the M2_2-16 peptide interestingly formed micelles without any peptidyl or lipid modifications. Because this unmodified peptide self-assembled on its own, it enabled the decoupling of the effect of micellization on immunogenicity from the incorporation of non-vaccine components such as the addition of a lipid moiety (Palm₂K) and a zwitterion-like peptide block ((KE)₄). The enclosed work shows that M2_2-16 peptidyl micelles had some characteristic differences in shape, critical micelle concentration, and secondary structure when compared to M2_2-16 peptide amphiphile micelles, which produced a few differences in murine antibody responses. These results suggest that peptide amphiphile micelles could be leveraged as a one-dose vaccine, while either micelle formulation induced strong immunological responses with a prime-booster immunization regimen.