5 years ago

An LASV GPC pseudotyped virus based reporter system enables evaluation of vaccines in mice under non-BSL-4 conditions

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.

Publisher URL: www.sciencedirect.com/science

DOI: S0264410X1731037X

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