Heterologous Prime-Boost Schedules of Replication-Defective Adenovirus Serotype 26 and Modified Vaccinia Virus Ankara Vector Vaccines Expressing Ebola Virus Glycoprotein Are Immunogenic and Well Tolerated in Healthy Adults

Background:

We report the preliminary data from the first-in-human safety and immunogenicity assessment of a candidate Ebola vaccine strategy incorporating a monovalent Adenovirus-type 26 vector vaccine and a multivalent Modified Vaccinia Ankara vector.

Methods:

We conducted a phase 1, randomized, placebo-controlled, observer-blind trial assessing replication-defective Ad26.ZEBOV (dose 5x10¹⁰ vp) and MVA-BN-Filo (dose 1x10⁸ TCID₅₀) given in heterologous prime-boost vaccination schedules to 87 healthy adults in the UK. The interim analysis of safety and immunogenicity in 36 individuals is presented. Participants were randomly allocated in a 1:1 ratio to receive prime Ad26.ZEBOV/boost MVA-BN-Filo or prime MVA-BN-Filo/boost Ad26.ZEBOV at an interval of 4 weeks and further randomized in a 5:1 ratio to study vaccines or placebo. 

Results:

28 days following primary immunization, Ebola glycoprotein (GP) specific IgG responses were seen in 33.3% (95% C.I. 11.8 – 61.6) of MVA-BN-Filo recipients and 93.3% (68 – 99.8) of Ad26.ZEBOV recipients. 21 days post booster dose, Ebola GP IgG was detectable in all vaccine recipients, with geometric mean IgG levels of 10573 ELISA unit/mL (95% C.I. 6452 ­– 17327) in MVA-BN-Filo/Ad26.ZEBOV recipients compared to 4274 ELISA units/mL (95% C.I. 2350 – 7775) in Ad26.ZEBOV/MVA-BN-Filo recipients. Ebola-specific ELISpot T cell responses were highest at 7 days post boost, with 93.3% (68 – 99.8) of MVA-BN-Filo/Ad26.ZEBOV recipients and 86.7% (59.5 – 98.3) of Ad26.ZEBOV/MVA-BN-Filo recipients responding to vaccination. Fever occurred in only 2 vaccine recipients, both following an Ad26.ZEBOV booster. Following prime or boost MVA-BN-Filo immunization, transient local and systemic reactions were observed in 17/30 (56.7%) and 11/30 (36.7%) of participants respectively, compared with 27/30 (90%) for both local and systemic reactions following Ad26.ZEBOV.

Conclusion:

The use of these vaccines in either schedule was well-tolerated by healthy adult volunteers with induction of humoral and cellular immunity in the vast majority of vaccinees. This represents a promising new immunization strategy against Ebola. Phase 3 efficacy studies are planned to begin later this year in West Africa.