A recombinant vesicular stomatitis virus-based vaccine provides postexposure protection against Bundibugyo ebolavirus infection
Bundibugyo virus (BDBV) is the most recently discovered pathogenic species of ebolavirus, with mortality rates of 25% and 51% reported in two identified. BDBV infection is non-uniformly lethal in macaques. The lack of uniform lethality offers the opportunity for identification of biomarkers that correlate with positive and negative outcomes following infection that can help define mechanisms of pathogenesis and potentially serve as guides for clinical care. In both the treatment and control groups, ~58% survived infection, an increase over lethality seen in historical controls. There was no differential advantage of the BDBV GP expressing vaccine, suggesting a general effect of rVSV. Our transcriptomic analysis identified strong initial responses to infection and treatment in all animals. This response returned to baseline in animals with mild disease by day 7. In animals with severe disease, fatal cases could be predicted beginning at day 5 post infection based on the expression of 5 circulating mRNAs. This study suggested a nonspecific effect of treating NHPs with VSV-based vectors as a postexposure therapy following BDBV infection and identified potential biomarkers of outcome. Overall design: Seven cynomolgus macaques were challenged by intramuscular injection in the left quadriceps with a 1,000 PFU target dose of BDBV challenge stock (the actual dose was 913 PFU). Approximately 20-23 minutes post challenge, six animals were treated with ~ 2X10^7 PFU of rVSV?G/BDBV-GP via i.m. injection. The inoculation was equally distributed between the left and right quadriceps. Animals were monitored for viremia and clinical signs of illness (temperature, weight loss, changes in blood count, and blood chemistries) during the treatment and BDBV challenge portions of the study. Blood was collected on days 0, 1, 5, 7, 9, 12, 15, 21, and 28 post challenge. Samples were also collected on the day of euthanasia.