Unprecedented short-term in vivo protection in mice with a single immunization of a DNA GP vaccine against heterologous mouse-adapted Ebola virus challenge

Abstract

Abstract The recent Ebola outbreak in West Africa is a reminder that correlates of protection against filovirus infection are still not well understood. DNA vectors are a serology-independent platform that allow for vector re-administration with minimal side-effects. We designed a new micro-consensus DNA vaccine that expresses a Zaire Ebolavirus (EBOV) glycoprotein (GP) based on 2002–2008 EBOV outbreak strains. This novel glycoprotein is 3% distant from the GP expressed by the 1976 EBOV Mayinga outbreak strain. The optimized GP DNA vaccine was administered in mice by intramuscular injection followed by electroporation (IM-EP) and elicited strong total IgG antibody and T cell responses. To assess protection from challenge, we administered the GP DNA vaccine or pVax1 control (40ug) to BALB/c mice (n=10/group) by IM-EP at days 0, -7, -14, or -28 before lethal challenge (1000LD50) with a mouse-adapted EBOV Mayinga strain. Importantly we observed 100% protection against the lethal heterologous challenge when the DNA vaccine was administered 28 days before challenge illustrating the potency of this vaccine in this model. More importantly, we observed 100% protection and 90% protection when the DNA vaccine was administered at days -14 and day -7, respectively. Most surprising was the observation of 40% survival in the group that received vaccine at Day 0 (2–3 hours) before challenge. Rapid, short-term protection has been previously observed with a VSV-ZEBOVGP viral vector vaccine but never before with a DNA vaccine. The data suggests that protection in mice following administration of a heterologous DNA vaccine can be afforded by mechanisms independent solely of antibody titers. Ongoing studies are underway in NHPs to investigate these findings.