title: A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.
abstract: BACKGROUND
  Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models.
  Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever.
  
  
  CONCLUSIONS
  Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.
authors.affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Safronetz
authors.affiliation: Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Chad
authors.initials: C
authors.lastname: Mire
authors.affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Kyle
authors.initials: K
authors.lastname: Rosenke
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Elaine
authors.initials: E
authors.lastname: Haddock
authors.affiliation: Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Geisbert
authors.affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000354:Africa, Western; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D014644:Genetic Variation; D006168:Guinea Pigs; D006801:Humans; D007835:Lassa Fever / Q000517:prevention & control*; D007836:Lassa virus / Q000235:genetics* / Q000276:immunology; D008251:Macaca; D014611:Vaccination / Q000379:methods; D018116:Vesiculovirus / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D014760:Viral Fusion Proteins; D014765:Viral Vaccines