Recombinant vesicular stomatitis virus vaccine elicits anti-Ebola seroconversion

1. By day 28, all recipients of a recombinant vesicular stomatitis virus (rVSV) vaccine, at each of the three doses tested, demonstrated seroconversion against an Ebola virus glycoprotein.

2. Anti-Ebola glycoprotein titers were higher in patients who received a 20 million or 100 million plaque forming unit (PFU) dose than in patients who received the 3 million PFU dose.

Evidence Rating Level: 2 (Good)       

Study Rundown: The Ebola virus outbreak of 2014 has prompted renewed interest in development of a vaccine that could be used for pre-exposure prophyaxis. This study tested the use of a rVSV live attenuated recombinant virus vaccine that was genetically engineered to replace the VSV glycoprotein with that of the Zaire strain of Ebola virus (ZEBOV). The results of two placebo-controlled, dose-escalation trials of the rVSV-ZEBOV are reported by this paper.

A total of 78 healthy adults, 39 at each site, were enrolled into groups of 13. In each group, 3 participants were randomly assigned to receive placebo and 10 were assigned to receive 3 million, 20 million, or 100 million PFU of the rVSV-ZEBOV vaccine. All the vaccinated volunteers had detectable vaccine viremia at the first visit after vaccination, but viremia was undetectable by day 14 in all vaccines tested at that time point. 80% of volunteers who received 3 million PFU, 95% of volunteers who received 20 million PFU, and 90% of volunteers who received 100 million PFU had undergone seroconversion by day 14. 100% of vaccinated volunteers underwent seroconversion by day 28, as assessed by ELISA against the ZEBOV glycoprotein.

These findings indicate that the rVSV-ZEBOV vaccine may be a promising agent for Ebola virus pre-exposure prophylaxis, as it elicited an antibody response by a single dose. The similarity between the 20 million PFU dose and 100 million PFU dose support the selection of 20 million PFU as the appropriate dose for further clinical trials. These results are strengthened by the two-center, placebo-controlled, dose-escalation design of the study, but may be limited by underpowering that limits its ability to detect differences in the incidence of adverse events between groups.

Click to read the study, published today in NEJM

Relevant Reading: Ebola virus vaccines: an overview of current approaches

In-Depth [prospective cohort]: This was a phase 1, double-blind, placebo-controlled, dose-escalation trial of rVSV-ZEBOV vaccine. On day 14, the groups that received a dose of 20 million PFU or 100 million PFU had higher geometric titers against the ZEBOV glycoprotein than the group that received a dose of 3 million PFU (857 and 888 vs 283; p = 0.008 and p = 0.02, respectively) and this was also seen on day 28 (4079 and 4079 vs 1300; p = 0.001 and p < 0.001, respectively). There was no significant difference in the mean titer between the group that received a dose of 20 million PFU and the group that received a dose of 100 million PFU.

Image: PD

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