Recombinant Ebolavirus antigens from insect cells are potent immunogens inducing cellular and humoral immunity in rodents and non-human primates and provide protection against virus challenge (P4325)

Abstract

Soluble recombinant Filovirus surface glycoproteins (GP) and matrix proteins (VP24 and VP40) were generated in the Drosophila S2 cell expression system and purified by immunoaffinity chromatography. The immunogenicity of individual recombinant Zaire ebolavirus (ZEBOV) subunits and admixtures with or without adjuvants was evaluated in mice, guinea pigs and macaques. Strong antigen-specific IgG responses were observed, includng Ebola virus neutralization responses. In mice and macaques subunit proteins were shown to elicit cell mediated immunity, as significant B- and T-cell stimulation was observed in immune lymphocytes after antigen re-stimulation. Analysis of secreted cytokines in batch-cultured, antigen-stimulated splenocytes or PBMC’s demonstrated Th1 and Th2 type responses. Vaccine candidates were tested in mice and guinea pigs for direct protection against challenge with species-adapted ZEBOV. All vaccine formulations containing ZEBOV GP were protective in mice and serum transfer from such animals into naïve mice demonstrated that humoral immunity alone can be fully protective. Furthermore, the transfer of immune splenocytes into naïve mice showed that recombinant GP and VP24 subunits elicit functional T cell responses that lead to protection against live virus challenge. In guinea pigs, lead vaccine formulations consistently produced high antibody responses and demonstrated 100% protective efficacy in the ZEBOV challenge model.