Lassa virus (LASV) causes a severe hemorrhagic
fever endemic throughout western Africa. Because of the ability to cause lethal disease in humans, limited treatment options, and potential as a bioweapon, the need for
vaccines to prevent LASV epidemic is urgent. However, LASV
vaccine development has been hindered by the lack of appropriate small animal models for efficacy evaluation independent of biosafety level four (BSL-4) facilities. Here we generated an LASV-
glycoprotein precursor (GPC)-pseudotyped Human immunodeficiency virus containing
firefly luciferase (Fluc) reporter gene as surrogate to develop a bioluminescent-imaging-based BALB/c mouse model for one-round
infection under non-BSL-4 conditions, in which the bioluminescent intensity of Fluc was utilized as endpoint when evaluating
vaccine efficacy. Electron microscopy analysis demonstrated that LASV GPC pseudotyped virus appeared structurally similar to native virion. Meanwhile, we constructed
DNA vaccine (pSV1.0-LASVGPC) and pseudoparticle-based
vaccine (LASVpp) that displayed conformational GPC
protein of LASV strain Josiah to vaccinate BALB/c mice using intramuscular electroporation and by intraperitoneal routes, respectively. Vaccinated mice in LASVpp alone and
DNA prime+LASVpp boost schedules were protected against 100 AID50 of LASV pseudovirus challenge, and it was found that in vivo efficiencies correlated with their anti-LASV neutralizing activities and MCP-1
cytokine levels in serum sampled before
infection. The bioluminescence pseudovirus
infection model can be useful tool for the preliminary evaluation of immunogenicity and efficacy of
vaccine candidates against LASV outside of BSL-4 containments, and the results with pseudoparticle-based
vaccine provided very helpful information for LASV
vaccine design.