Ebola virus vaccine based on 2014 epidemic strain shown to be safe and immunogenic

1. A randomized, double-blind, placebo-controlled phase 1 trial testing a new Ebola virus vaccine specific to the 2014 Zaire Guinea strain was determined to be safe, with mild pain at the injection site being the most common adverse reaction and no serious adverse events reported in 28 days of follow-up.

2. The vaccine was immunogenic with specific antibody responses recorded beginning at 14 days after vaccination.

Evidence Rating Level: 1 (Excellent)

Study Rundown: With the largest ever Ebola virus epidemic in 2014, several countries have attempted to create a vaccine to control the spread of the disease. All previous vaccines being developed have been based on the strain from the 1976 outbreak in Zaire, however, the Guinea Zaire variant strain behind the 2014 epidemic was found to share only 97.6% similarity to the 1976 Zaire strain. This randomized, double-blind, placebo-controlled phase 1 trial assessed the safety and immunogenicity of a new adenovirus type-5 vector based vaccine against the 2014 Zaire Guinea strain.

The results showed that the Ebola vaccine was safe and immunogenic in healthy adults. No serious adverse events were reported in 28 days of follow-up, and mild pain at the injection site was the most common adverse reaction. Ebola-specific antibody responses were noted to significantly increase beginning at day 14 in both the low-dose and high-dose vaccine groups, with no specific antibody response in the placebo group. T-cell responses peaked at 14 days in both vaccine groups, with significantly higher responses in the high-dose group compared to the low-dose group. This study was strengthened by additionally testing the vaccine against pre-existing neutralizing adenovirus type-5 vector antibodies found in participants, however it was limited by only reporting results up to 28 days after vaccination.

This study was funded by China National Science and Technology, Beijing Institute of Technology, and Tianjin CanSino Biotechnology

Click to read the study, published today in The Lancet

Relevant Reading: Emergence of Zaire Ebola virus disease in Guinea

In-Depth [randomized controlled trial]: 120 healthy adults aged 18-60 years without HIV infection or hepatorenal dysfunction were enrolled in the study conducted at a site in China. Participants were randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine (n=40). Participants were monitored for any adverse reactions for six hours after vaccine administration then self-recorded any adverse events for the next 28 days, and returned on days 3, 7, 14, and 28 for a safety assessment and blood samples to measure hematological, hepatic, and renal function, as well as antibody and T-cell responses. The primary safety endpoint was occurrence of adverse reactions within 7 days of vaccine administration and the primary immunogenicity endpoint was Ebola specific ELISA antibody titers to the 2014 Zaire Guinea strain and T-cell responses at 28 days.

82 (68%) participants reported at least one solicited adverse reaction within 7 days, which differed significantly between groups (19 [48%] in placebo group, 27 [68%] in low-dose group, 36 [90%] in high-dose group; p=0.0002). The most common adverse reaction was mild pain at the injection site (8 [20%] in placebo group, 14 [35%] in low-dose group, 29 [73%] in high-dose group; p<0.0001). No serious adverse events were reported during 28 days of follow-up. No specific antibody response to Ebola was detected within 7 days in all groups, but both vaccine groups recorded significant responses beginning at day 14, while no specific response was measured in the placebo group. T-cell responses peaked in both vaccine groups at day 14, and were significantly higher in the high-dose group than low-dose group at both day 14 and 28. Additionally, pre-existing neutralizing antibodies to adenovirus type-5 vectors were found in approximately 60% of each group’s participants, however, but the high-dose vaccine provided sufficient immunogenicity to overcome the negative effects of pre-existing antibodies.

Image: PD

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