Adenoviral vector-based vaccine is fully protective against lethal Lassa fever challenge in Hartley guinea pigs

Junki Maruyama, Elizabeth J. Mateer, John T. Manning, Rachel Sattler, Alexey V. Seregin, Natalya Bukreyeva, Frank R. Jones, Joseph P. Balint, Elizabeth S. Gabitzsch, Cheng Huang, Slobodan Paessler

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Lassa virus (LASV), the causative agent of Lassa fever (LF), was first identified in 1969. Since then, outbreaks in the endemic countries of Nigeria, Liberia, and Sierra Leone occur on an annual basis resulting in a case-fatality rate of 15–70% in hospitalized patients. There is currently no licensed vaccine and there are limited animal models to test vaccine efficacy. An estimated 37.7 million people are at risk of contracting LASV; therefore, there is an urgent need for the development of a safe, effective vaccine against LASV infection. The LF endemic countries are also inflicted with HIV, Ebola, and malaria infections. The safety in immunocompromised populations must be considered in LASV vaccine development. The novel adenovirus vector-based platform, Ad5 (E1-,E2b-) has been used in clinical trial protocols for treatment of immunocompromised individuals, has been shown to exhibit high stability, low safety risk in humans, and induces a strong cell-mediated and pro-inflammatory immune response even in the presence of pre-existing adenovirus immunity. To this nature, our lab has developed an Ad5 (E1-,E2b-) vector-based vaccine expressing the LASV-NP or LASV-GPC. We found that guinea pigs vaccinated with two doses of Ad5 (E1-,E2b-) LASV-NP and Ad5 (E1-,E2b-) LASV-GPC were protected against lethal LASV challenge. The Ad5 (E1-,E2b-) LASV-NP and LASV-GPC vaccine represents a potential vaccine candidate against LF.

Original languageEnglish (US)
Pages (from-to)6824-6831
Number of pages8
JournalVaccine
Volume37
Issue number45
DOIs
StatePublished - Oct 23 2019

Keywords

  • Adenovirus vector
  • Lassa fever
  • Lassa virus
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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