Distinct immunogenicity and efficacy of poxvirus-based vaccine candidates against Ebola virus expressing GP and VP40 proteins

Adrián Lázaro-Frías, Sergio Gómez-Medina, Lucas Sánchez-Sampedro, Karl Ljungberg, Mart Ustav, Peter Liljeström, César Muñoz-Fontela, Mariano Esteban, Juan García-Arriaza

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Zaire and Sudan ebolavirus species cause a severe disease in humans and nonhuman primates (NHPs) characterized by a high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013 to 2016 outbreak in West Africa highlighted the need for EVD-specific medical countermeasures. Here, we 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), proinflammatory 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 ebolavirus were differentially induced by these vectors, which were mainly of the IgG1 and IgG3 isotypes. Remarkably, an MVA-EBOV construct coexpressing GP and VP40 protected chimeric mice challenged with EBOV to a greater extent 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.

Original languageEnglish
Article numbere00363-18
JournalJournal of Virology
Volume92
Issue number11
DOIs
StatePublished - 1 Jun 2018
Externally publishedYes

Keywords

  • Ebola
  • GP
  • Immunogenicity
  • MVA
  • Mice
  • Poxvirus
  • Protection
  • VP40

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