Lipid nanoparticle mRNA vaccine expressing Ebola virus glycoprotein elicits strong humoral response and protection against challenge compared to alternative nucleotide platforms 9156

Description Ebola virus (EBOV) is the causative agent behind Ebola virus disease (EVD), characterized by hemorrhagic fever and a high case fatality rate. Current treatments for EVD are limited to monoclonal antibodies or gold-standard recombinant vesicular stomatitis virus (rVSV)-vectored vaccine. However, protection and efficacy comparisons with alternative nucleotide platforms are understudied. Here we developed a lipid nanoparticle (LNP) mRNA vaccine against EBOV glycoprotein (EBOVgp) and queried protection in mice from prime-boost LNP-mRNA versus rVSV-EBOVgp or a DNA vaccine. We vaccinated WT C57BL/6 mice with 5mg/animal of mRNA-LNP, boosted at D28, and either analyzed at D35 or challenged with an infectious model of EBOV at D35 or D57. While both mRNA-LNPs and rVSV-EBOVgp elicited similar total serum IgG levels, the LNPs generated higher neutralizing titers. Ab targeting of EBOV was evaluated between platforms via PepSeq. Following confirmation of mRNA-LNP immunogenicity, we performed two lethal challenge experiments: 1) IFNAR-/- mice + VSV-EBOVgp infection model of EVD at ABSL-2, and 2) WT B6 mice with mouse adapted EBOV at ABSL-4. In both cases, mRNA LNP protected all mice from mortality and ablated symptoms. Our results suggest that an mRNA-LNP vaccine expressing EBOVgp induces a robust functional humoral response that protects against lethal EBOV challenge, warranting further development as a safe alternative to viral vectored vaccines. Funding Sources This work was supported by the Defense Threat Reduction Agency under the Rapid Assessment of Platform Technologies to Expedite Response (RAPTER) program (award no. HDTRA1242031).