Protection From Lethal Lassa Disease Can Be Achieved Both Before and After Virus Exposure by Administration of Single-Cycle Replicating Lassa Virus Replicon Particles

J Infect Dis. 2019 Sep 13;220(8):1281-1289. doi: 10.1093/infdis/jiz284.

Abstract

Lassa fever is a frequently severe human disease that is endemic to several countries in West Africa. To date, no licensed vaccines are available to prevent Lassa virus (LASV) infection, even though Lassa fever is thought to be an important disease contributing to mortality and both acute and chronic morbidity. We have previously described a vaccine candidate composed of single-cycle LASV replicon particles (VRPs) and a stable cell line for their production. Here, we refine the genetic composition of the VRPs and demonstrate the ability to reproducibly purify them with high yields. Studies in the guinea pig model confirm efficacy of the vaccine candidate, demonstrate that single-cycle replication is necessary for complete protection by the VRP vaccine, and show that postexposure vaccination can confer protection from lethal outcome.

Keywords: Lassa; postexposure; single-cycle replication; vaccine; virus replicon particle.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • A549 Cells
  • Africa, Western
  • Animals
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Female
  • Guinea Pigs
  • Humans
  • Immunization Schedule
  • Lassa Fever / prevention & control*
  • Lassa Fever / virology
  • Lassa virus / genetics
  • Lassa virus / immunology*
  • Lassa virus / isolation & purification
  • Male
  • Post-Exposure Prophylaxis / methods*
  • Replicon / immunology
  • Vaccination / methods*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vero Cells
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology

Substances

  • Vaccines, Synthetic
  • Viral Vaccines