Abstract
Recent outbreaks of emerging infectious diseases, such as Ebola virus disease (EVD), highlight the urgent need to develop effective countermeasures, including prophylactic vaccines. Subunit proteins derived from pathogens provide a safe source of antigens for vaccination, but they are often limited by their low immunogenicity. We have developed a multilamellar vaccine particle (MVP) system composed of lipid-hyaluronic acid multi-cross-linked hybrid nanoparticles for vaccination with protein antigens and demonstrate their efficacy against Ebola virus (EBOV) exposure. MVPs efficiently accumulated in dendritic cells and promote antigen processing. Mice immunized with MVPs elicited robust and long-lasting antigen-specific CD8+ and CD4+ T cell immune responses as well as humoral immunity. A single-dose vaccination with MVPs delivering EBOV glycoprotein achieved an 80% protection rate against lethal EBOV infection. These results suggest that MVPs offer a promising platform for improving recombinant protein-based vaccine approaches.