Pseudovirus Nanoparticles Displaying the Receptor-Binding Glycoprotein of Marburg Virus as Potential Vaccine Candidates

Background: The lack of a licensed vaccine against the deadly Marburg virus (MARV) calls for the development of a novel and effective vaccine strategy. Methods: We report here our development of three pseudovirus nanoparticles (PVNPs), each displaying a MARV-neutralizing glycoprotein (GP) segment of different lengths, as MARV vaccine candidates. These PVNPs, designated S-GP278, S-GP377, and S-GP486, were generated using our proprietary norovirus shell nanoparticle (SNP) platform. The PVNPs were evaluated for their production, self-assembly, morphology, structural properties, and immunogenicity. Results: Our data demonstrated that the three recombinant S-GP proteins, S-GP278, S-GP377, and S-GP486, can be produced at low cost using an E. coli expression system. The purified recombinant S-GP proteins self-assembled into PVNPs with high efficacy. Structural modeling of the S-GP1 PVNPs highlighted their key architectural features, consisting of an icosahedral inner shell and multiple trimeric GP structures displayed on the surface. Immunization of mice with the S-GP PVNPs elicited high titers of GP-specific antibodies, including IgG and IgA. Conclusions: Collectively, these data support the notion that the S-GP PVNPs may serve as potential MARV vaccine candidates worthy of further development.