Marburg virus glycoprotein mRNA vaccine is more protective than a virus-like particle-forming mRNA vaccine

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Abstract

Although virus-like particle (VLPs) vaccines were shown to be effective against several viruses, their advantage over vaccines which include envelope protein only is not completely clear, particularly for mRNA-encoded VLPs. We conducted a side-by-side comparison of the immunogenicity and protective efficacy of mRNA vaccines encoding for the Marburg virus (MARV) full-length GP delivered alone or as a VLP. Electron microscopy confirmed VLP formation when MARV GP and matrix protein VP40 co-expressed. We vaccinated guinea pigs with a two-component mRNA vaccine encoding for GP and VP40 (VLP) or GP alone. At the highest dose, both vaccines protected fully, although the VLP vaccine elicited a slightly lower humoral response than the GP-only group. However, at low doses, GP-only mRNA conferred 100% protection, whereas the VLP exhibited only partial protection. In mice, VLP mRNA induced a moderate preference for GP-specific CD8+ T cells responses, whereas the GP-only mRNA somewhat favored CD4+ T cell responses. Guinea pig whole blood RNA-seq revealed that the VLP vaccine down-regulated genes associated with various biological and metabolic processes, including the NF-κB signaling pathway, whereas the GP-only vaccine upregulated interferon signaling. Overall, the VLP mRNA vaccine was less immunogenic and protective, whereas the GP-only mRNA vaccine conferred robust protection by as little as one µg dose in guinea pigs.

Authors

Chandru Subramani, Michelle N. Meyer, Matthew A. Hyde, Margaret E. Comeaux, Haiping Hao, James E. Crowe Jr., Vsevolod L. Popov, Harshwardhan Thaker, Sunny Himansu, Andrea Carfi, Alexander Bukreyev