A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses

David Safronetz, Chad Mire, Kyle Rosenke, Friederike Feldmann, Elaine Haddock, Thomas Geisbert, Heinz Feldmann

Research output: Contribution to journalArticle

38 Citations (Scopus)

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. Methodologies/principle findings: 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/significance: 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.

Original languageEnglish (US)
Article numbere0003736
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number4
DOIs
StatePublished - Apr 17 2015

Fingerprint

Lassa Fever
Lassa virus
Vesicular Stomatitis
Macaca
Guinea Pigs
Vaccines
Viruses
Nigeria
Viral Hemorrhagic Fevers
Animal Models
Liberia
Sierra Leone
Mali
Morbidity
Active Immunotherapy
Genetic Heterogeneity
Mortality
Infection
Gold

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses. / Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz.

In: PLoS Neglected Tropical Diseases, Vol. 9, No. 4, e0003736, 17.04.2015.

Research output: Contribution to journalArticle

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