Abstract
Lassa virus (LASV), which causes deadly Lassa fever (endemic in Western Africa), is a priority pathogen and a global health threat. Current vaccine candidates protect LASV-challenged animals through T cell immunity or non-neutralizing IgG/Fc receptor-mediated functions in the absence of potent neutralization. Neutralizing antibodies (nAbs), applied through passive immunization, also provide broad and complete protection against LASV. Rational design of LASV glycoprotein complex (GPC), the primary target for adaptive immunity, overcomes prior challenges to elicitation of nAbs caused by the dense glycan shield, metastability, and heterogeneity of GPC. Well-engineered GPC immunogens, in combination with advanced immunization methods and existing clinical trial phase vaccine candidates, provide a possibility to infuse neutralizing activity into complementary mechanisms of immune protection delivered by LASV vaccination.