A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model

Vaccine. 2019 Aug 23;37(36):5404-5413. doi: 10.1016/j.vaccine.2019.07.023. Epub 2019 Jul 19.

Abstract

Lassa fever remains the most imported viral haemorrhagic fever in Europe and is responsible for 5000 deaths per year throughout Western Africa. There is no vaccine and treatment is often ineffective. We have developed a vaccine based on modified Vaccinia Ankara expressing the nucleoprotein from Lassa virus (MVALassaNP). This study investigated the immunogenicity (in mice) and efficacy (in guinea pigs) of the MVALassaNP vaccine as a prime/boost or single vaccination regime. ELISA and ELISpot assays confirmed humoral and T-cell immunity following both a prime and prime/boost vaccination, with the prime/boost regime producing a statistically increased response compared to a prime only vaccine (P < 0.0001). The vaccine offered protection in guinea pigs against disease manifestations after challenge with virulent Lassa virus. Clinical signs, weight loss and temperature increases were observed in all animals receiving a control MVA vaccine, after challenge with Lassa virus. In contrast, no clinical signs, fever or weight loss were observed in any of the MVALassaNP vaccinated animals demonstrating that both a single immunisation, and prime/boost regime confer protection against disease progression. In conclusion, the MVALassaNP vaccine candidate elicits an immune response, demonstrates efficacy against Lassa virus disease and is suitable for further preclinical and clinical development.

Keywords: Efficacy; Immunogenicity; Lassa; Modified Vaccinia Ankara (MVA); Nucleoprotein; Recombinant vaccine; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Guinea Pigs
  • Lassa virus / immunology*
  • Nucleoproteins / immunology*
  • Vaccination
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use
  • Vaccinia / immunology*
  • Vaccinia / prevention & control*
  • Vaccinia virus / immunology
  • Vaccinia virus / pathogenicity

Substances

  • Nucleoproteins
  • Vaccines, Synthetic