A phase Ib, placebo-controlled randomized clinical trial of the Ebolavirus DNA vaccine candidate INO-4201 followed by electroporation as booster vaccination in healthy, rVSVΔG-ZEBOV-GP-primed volunteers (Boost-EBOV).

OBJECTIVES

Nearly a million people have received the recombinant vesicular stomatitis virus-based vaccine expressing the surface glycoprotein of Ebola virus (rVSVΔG-ZEBOV-GP), whose immune durability is unknown. We evaluated the safety and immunogenicity of the DNA vaccine candidate INO-4201 in volunteers primed with the rVSVΔG-ZEBOV-GP vaccine.

METHODS

This investigator-initiated phase Ib double-blind, placebo-controlled, single-centre trial randomly assigned healthy adults (≥18 years) primed with rVSVΔG-ZEBOV-GP to intradermal INO-4201 (1 mg) or placebo (4:1), both followed with electroporation. The coprimary outcome was incidence of adverse events at 14 days and geometric mean EBOV-GP-binding antibody titres (GMT) at 28 days (clinicaltrials.gov NCT04906629).

RESULTS

Forty-six participants were enrolled. Median age was 52 years (interquartile range 44-57); 26 (57%) were male. Thirty-six participants received INO-4201 and 10 participants received placebo. No serious adverse events occurred. There was little reactogenicity. At 14 days, 20 of 36 (56%) vaccinees versus 5 of 10 (50%) placebo recipients (relative risk 1.11 [95% CI 0.56-2.20]) experienced adverse events. Peak T-cell responses were significantly increased in INO-4201 recipients (median percentage of CD4 cells producing interferon-gamma at postboost peak versus day 0: 0.09 [range 0.00-14.48] versus 0.00 [0.00-1.33], p 0.004). Filovirus Animal Non-Clinical Group-based EBOV-GP-binding titres were significantly higher after boosting for vaccinees at all time points (GMT at 4 weeks versus day 0: 3221.7 [95% CI 2629.8-3946.8] vs 704.3 [513.8-965.3]). Neutralizing antibody titres were also significantly higher after boosting for vaccinees at all time points measured (GMT at 4 weeks versus day 0: 21.3 [95% CI 13.8-32.7] versus 2.4 [1.5-3.9]).

CONCLUSIONS

In adults primed with rVSVΔG-ZEBOV-GP, INO-4201 demonstrated favourable safety and significant immunogenicity.