title: Evaluation of Lassa virus vaccine immunogenicity in a CBA/J-ML29 mouse model.
abstract: Lassa fever (LF) is one of the most prevalent viral hemorrhagic fevers in West Africa responsible for thousands of deaths annually. The BSL-4 containment requirement and lack of small animal model to evaluate Lassa virus (LASV)-specific cell-mediated immunity (CMI) complicate development of effective LF vaccines. Here we have described a CBA/J-ML29 model allowing evaluation of LASV-specific CMI responses in mice. This model is based on Mopeia virus reassortant clone ML29, an attractive immunogenic surrogate for LASV. A single intraperitoneal (i.p.) immunization of CBA/J mice with ML29 protected animals against a lethal homologous intracerebral (i.c.) challenge with 588 LD(50). The ML29-immunized mice displayed negligible levels of LASV-specific antibody titers, but LASV-specific CMI responses were detectable early and peaked on day 8-10 after immunization. A T cell cytotoxicity assay in vivo showed a correlation between LASV-specific cytotoxicity and the timing of protection induced by the ML29 immunization. Notably, CBA/J mice that received CD8+ T cell-depleted splenocytes from ML29-immunized donors all succumbed to a lethal i.c. challenge, demonstrating that CD8+ T cells are critical in protection. The CBA/J-ML29 model can be useful immunological tool for the preliminary evaluation of immunogenicity and efficacy of vaccine candidates against LASV outside of BSL-4 containment facilities.
authors.affiliation: Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD 21201, United States. mgoic001@umaryland.edu
authors.forename: Marco A
authors.initials: MA
authors.lastname: Goicochea
authors.forename: Juan C
authors.initials: JC
authors.lastname: Zapata
authors.forename: Joseph
authors.initials: J
authors.lastname: Bryant
authors.forename: Harry
authors.initials: H
authors.lastname: Davis
authors.forename: Maria S
authors.initials: MS
authors.lastname: Salvato
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018049:Arenaviruses, Old World / Q000276:immunology*; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D007835:Lassa Fever / Q000517:prevention & control*; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008808:Mice, Inbred CBA; D016865:Reassortant Viruses / Q000276:immunology; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014765:Viral Vaccines