Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection

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.

Advances in vaccine delivery systems against viral infectious diseases

“…A lipid and biopolymer hybrid nanoparticle was investigated for the subcutaneous delivery of the Ebola virus spike glycoprotein [81]. The hybrid nanoparticles consisted of various lipids, including 1,2-dioleoyloxy-3-(trimethylammonium) propane, 1,2-dioleoyl-sn-glycero-3-phosphocholine, and maleimide-functionalized N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propan-1-aminium, which were crosslinked with thiolated hyaluronic acid.…”

Organic and inorganic nanoparticle vaccines for prevention of infectious diseases

“…Moon et al demonstrated that when PLGA conjugated-malaria antigen, VMP001, was encapsulated within lipid membrane, these PLGA-lipid nanoparticles elicited higher humoral responses in vivo with 10-fold less amount of soluble protein vaccine dose and sustained similar antibody titers for up to 180 days [46]. Similarly, a lipid-polymer hybrid multilamellar vaccine particle (MVP), composed of cationic lipidhyaluronic acid, crosslinked with Ebola virus (EBOV) glycoprotein, generated long-lasting antigen-specific CD8+ and CD4+ T cell responses, and a single dose of MVP vaccination protected 80% of mice against EBOV infection [18].…”

Biomimetic Nanomaterial Strategies for Virus Targeting: Antiviral Therapies and Vaccines

“…have also expanded on the ICMV strategy and developed lipid–polymer hybrid multilamellar vaccine particles (MVP) to incorporate Ebola virus antigen as well. [ 164 ] In this case, MVP immunization generated strong and durable antigen‐specific antibody and immune cell responses in mice, and single‐dose immunization protected 80% of mice from lethal Ebola virus infection. By contrast, an ICMV‐based vaccine only protected 40% of mice and the difference in vaccine‐mediated immune protection was suggested to arise from the greater antigen‐specific T cell response elicited by the MVP vaccine.…”