The 2014/2015 Ebola epidemic in West Africa claimed over eleven thousand lives and highlighted our under preparedness to counter emerging viral epidemics. A lead live replicating recombinant vaccine (rVSV-ZEBOV) whose deployment was expedited during the 2014/2015 Ebola epidemic was shown to be efficacious but questions have been raised with regards to its safety. To provide a safer alternative, we set out to develop a subunit vaccine candidate based on a soluble version of the recombinant Ebola glycoprotein (GP) that is stabilized in its pre-fusion conformation and has the potentially cytotoxic mucin-like and transmembrane domains removed. BALB/c mice were immunized via NanopatchTM (NP) microneedle delivery or intradermal injection. We then assessed the antibody response elicited against the live Ebola virus (Zaire strain) using facilities at CSIRO’s Australian Animal Health Laboratories in Geelong (AAHL).
The stabilized Ebola GP was recognized by a panel of highly neutralizing antibodies, indicating both the GP1/2 and glycan cap domains are available and presented in the desired conformation. Mouse sera showed promising plaque reduction neutralization titres following vaccinations (PRNT50 = ~1/50 sera dilution). We also showed that this candidate vaccine is thermostable, retaining significant antigenicity after extended incubation at 37°C. Immunization with the stabilized Ebola GP elicited a strong neutralizing immune response, indicative of protection. Long term stability indicates this vaccination strategy may not require cold chain transport. Furthermore, the removal of known cytotoxic domains and the absence of replicative elements ensures that this vaccine will have a safer profile than live recombinant vaccines. Taken together, our results suggest that this vaccine may represent a safer alternative strategy to combat future Ebola outbreaks.