In November 2014, two candidate Ebola virus vaccines were in the late stages of phase 1 testing, the chimpanzee adenovirus 3 (ChZ) – based vaccine and the recombinant Vesicular Stomatitis virus (rVSVdeltaG-ZEBOV GP) – based vaccine. In order to rapidly evaluate these vaccines, a 28,170 subject randomized, placebo-controlled trial aimed at preventing Ebola virus disease (EVD) that included both vaccines was designed. As the number of new cases declined to a level that a phase 3 study was no longer feasible the study was converted to a 1,500 subject phase 2 safety and immunogenicity trial.
Consenting volunteers ≥18 years were randomized to saline or one of the two experimental vaccines. Temperature > 38º C, history of EVD, pregnancy and breastfeeding were exclusions. Follow-up visits occurred at week 1, month 1, month 2 and then every 2 months thereafter through 12 months. Blood was collected for antibody measurements at baseline, week 1, month 1 and months 6 and 12. Chi-square tests were used to compare each vaccine versus the placebo group for injections site reactions, targeted symptoms, and antibody responses.
From February 2015 through April 2015, 1,500 volunteers were enrolled at Redemption Hospital in Monrovia, Liberia (500 per group). Median age was 30 years and 37% were women. 0.7% reported recent contact with a patient with Ebola; 4.6% reported working in a job that required contact with Ebola patients. The percentages of participants with positive serostatus for HIV and syphilis at baseline were 5.2% and 5.1%, respectively. Overall follow-up visit attendance has exceeded 98%. Differences with placebo in injection site reactions, targeted symptoms (headache, muscle pain, feverishness, fatigue) and lymphocyte counts were noted at week 1, but not month 1 for both vaccines. Antibodies, measured using the FANG ELISA assay for 50% of participants, show that 8% had an antibody response to Ebola at baseline. Excluding these individuals, an antibody response at month 1 was noted in >85% of participants in each of the vaccine arms and <10% of participants in the placebo arm (p<0.001)
It is possible to conduct a well-designed, randomized, placebo-controlled trial in the middle of an epidemic outbreak. Both vaccines were demonstrated to be safe and immunogenic. A number of individuals without a known history of Ebola virus disease were found to have evidence of past infection with Ebola. The prevalence of HIV-1 in this cohort is higher than expected.