A single immunization with optimized DNA vaccines protects against lethal Ebola virus challenge in mice (VAC8P.1057)

Abstract

Abstract Ebola is a hemorrhagic fever virus that is responsible for the severe, ongoing outbreak in West Africa that has infected >20000 people, exhibiting >37% mortality. Infection control has been complicated by a lack of approved vaccines and therapies and recent figures suggest that the outbreak is more severe than previously thought. We generated 3 DNA vaccines expressing Zaire ebolavirus (EBOV) glycoprotein (GP): 2 vaccines designed on consensus alignments of EBOV GPs (1976-2014) and a 3rd matched construct to a 2014 Guinea strain. BALB/c mice received 40ug of each vaccine, delivered by IM injection followed by electroporation. Strong T cell responses were detected for all 3 vaccines, including GP-specific CD4+ and CD8+ T cells. To broaden efficacy against emerging EBOV strains, we also co-administered DNA vaccines in 2 or 3 construct formulations. Groups of 10 BALB/c mice were challenged with a lethal dose of a heterologous mouse-adapted Mayinga 1976 EBOV strain. The two consensus DNA vaccines, and combinations of 2 and 3 vaccines were 100% protective in mice. The matched vaccine afforded 90% protection. Total GP-specific IgG antibody levels were high in all surviving animals and low in unprotected animals suggesting that titers may indicate therapeutic efficacy. All three DNA vaccines are immunogenic and no antigen interference was observed. These experiments in mice support further studies in non-human primates towards continued development of this potential vaccine platform.