Intradermal Delivery of INO-4201 Drives Robust Ebola Glycoprotein Specific Humoral and Cellular Immune Responses in Healthy Volunteers in an Open Label Phase I Trial

Abstract

The most recent Ebola outbreak in West Africa resulted in over 28,000 suspected cases of infection and over 11,000 deaths. As no specific immune correlate has been associated with protection against Ebola to date, the development of a vaccine that generates robust humoral and cellular immune responses may be the best approach to achieve full protection. INO-4201 is a plasmid-based prophylactic vaccine targeting Zaire Ebola glycoprotein (GP), designed to prevent Ebola infection. INO-4201 encodes a consensus antigen that encompasses genetic variability from previous outbreak strains to broaden immune coverage for divergent Ebola virus variants. Intradermal (ID) administration of a 2 or 3-dose regimen of INO-4201 followed by in vivo electroporation with the CELLECTRA® device was well tolerated in 140 healthy volunteers with no related Grade 3 or Grade 4 SAEs reported. INO-4201 induced robust Ebola GP-specific antibody and T cell responses in the healthy volunteers. The majority of patients seroconverted, as gauged by binding ELISA after only 2 doses of INO-4201. EBOV GP specific T cell response were assessed by Interferon gamma (IFNγ) ELISpot revealing a mean peak response magnitude of 295 SFU per 106 PBMCs. Intracellular cytokine staining indicated that immunization with INO-4201 drove statistically significant increases in the production of IFNγ or Tumor Necrosis Factor alpha in both the CD8+ T cell compartment (p=0.001) and CD4+ T cell compartment (p=0.004). ID administration of INO-4201 using the CELLECTRA® device was well tolerated and immunogenic as assessed by both humoral and cellular EBOV GP-specific immunoassays supporting INO-4201 as a strong candidate for further clinical development of a prophylactic Ebola vaccine.