Distinct Immunogenicity and Efficacy of Poxvirus-based Vaccine Candidates against Ebola Virus expressing GP and VP40 Proteins

Zaire and Sudan ebolavirus species cause a severe disease in humans and non-human primates (NHPs) characterized by high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013-2016 outbreak in West Africa highlighted the need of EVD-specific medical countermeasures. Here, we have generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA), expressing either the virus glycoprotein (GP) or GP together with the virus protein 40 (VP40) forming virus-like particles (VLPs). In a human monocytic cell line the different MVA vectors (termed MVA-EBOVs and MVA-SUDVs) triggered robust innate immune responses, with production of beta interferon (IFN-β), pro-inflammatory cytokines, and chemokines. Additionally, several innate immune cells, such as dendritic cells, neutrophils, and natural killer cells were differentially recruited in the peritoneal cavity of mice inoculated with MVA-EBOVs. After immunization of mice with a homologous prime/boost protocol (MVA/MVA) total IgG antibodies against GP or VP40 from Zaire and Sudan were differentially induced by these vectors, which were mainly of the IgG1 and IgG3 isotypes. Remarkably, an MVA-EBOV construct co-expressing GP and VP40 protected chimeric mice challenged with EBOV to higher extend than a vector expressing GP alone. These results support the consideration of MVA-EBOVs and MVA-SUDVs expressing GP and VP40 and producing VLPs as best-in-class potential vaccine candidates against EBOV and SUDV.See it on Scoop.it, via Viruses, Immunology & Bioinformatics from Virology.uvic.ca
Distinct Immunogenicity and Efficacy of Poxvirus-based Vaccine Candidates against Ebola Virus expressing GP and VP40 Proteins
Source: Viral Bioinformatics