A Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein (EBOV GP) Nanoparticle Vaccine with Matrix-M™ Adjuvant in Healthy Adults

BACKGROUND: Ebola virus (EBOV) epidemics pose a major public health risk. There currently is no licensed human vaccine against EBOV. The safety and immunogenicity of a recombinant EBOV glycoprotein (GP) nanoparticle vaccine formulated with or without Matrix-M™ adjuvant were evaluated to support vaccine development. METHODS: A phase 1, placebo-controlled, dose-escalation trial was conducted in 230 healthy adults to evaluate 4 EBOV GP antigen doses as single- or 2-dose regimens with or without adjuvant. Safety and immunogenicity were assessed through 1-year post-dosing. RESULTS: All EBOV GP vaccine formulations were well tolerated. Receipt of 2 doses of EBOV GP with adjuvant showed a rapid increase in anti-EBOV GP IgG titers with peak titers observed on Day 35 representing 498- to 754-fold increases from baseline; no evidence of an antigen dose-response was observed. Serum EBOV-neutralizing and binding antibodies using wild-type ZEBOV or pseudovirion assays were 3- to 9-fold higher among recipients of 2-dose EBOV GP with adjuvant, compared with placebo on Day 35, which persisted through 1 year. CONCLUSIONS: EBOV GP vaccine with Matrix-M adjuvant is well tolerated and elicits a robust and persistent immune response. These data suggest that further development of this candidate vaccine for prevention of EBOV disease is warranted. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov [NCT02370589]; anzctr.org.au [EBOV-H-101].