Vaccines (Mar 2022)

Protective CD8+ T Cell Response Induced by Modified Vaccinia Virus Ankara Delivering Ebola Virus Nucleoprotein

  • Alexandra Kupke,
  • Asisa Volz,
  • Erik Dietzel,
  • Astrid Freudenstein,
  • Jörg Schmidt,
  • Hosam Shams-Eldin,
  • Sylvia Jany,
  • Lucie Sauerhering,
  • Verena Krähling,
  • Michelle Gellhorn Serra,
  • Christiane Herden,
  • Markus Eickmann,
  • Stephan Becker,
  • Gerd Sutter

DOI
https://doi.org/10.3390/vaccines10040533
Journal volume & issue
Vol. 10, no. 4
p. 533

Abstract

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The urgent need for vaccines against Ebola virus (EBOV) was underscored by the large outbreak in West Africa (2014–2016). Since then, several promising vaccine candidates have been tested in pre-clinical and clinical studies. As a result, two vaccines were approved for human use in 2019/2020, of which one includes a heterologous adenovirus/Modified Vaccinia virus Ankara (MVA) prime-boost regimen. Here, we tested new vaccine candidates based on the recombinant MVA vector, encoding the EBOV nucleoprotein (MVA-EBOV-NP) or glycoprotein (MVA-EBOV-GP) for their efficacy after homologous prime-boost immunization in mice. Our aim was to investigate the role of each antigen in terms of efficacy and correlates of protection. Sera of mice vaccinated with MVA-EBOV-GP were virus-neutralizing and MVA-EBOV-NP immunization readily elicited interferon-γ-producing NP-specific CD8+ T cells. While mock-vaccinated mice succumbed to EBOV infection, all vaccinated mice survived and showed drastically decreased viral loads in sera and organs. In addition, MVA-EBOV-NP vaccinated mice became susceptible to lethal EBOV infection after depletion of CD8+ T cells prior to challenge. This study highlights the potential of MVA-based vaccines to elicit humoral immune responses as well as a strong and protective CD8+ T cell response and contributes to understanding the possible underlying mechanisms.

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