Evidence for cross-reactivity and protection against Bundibugyo virus disease after heterologous vaccination: a systematic review and meta-analysis

There are currently no approved vaccines or medical countermeasures for use in prevention or treatment of Bundibugyo virus disease. A critical question is whether the existing vaccines approved for use against Ebola virus disease could provide sufficient cross-reactivity and cross-protection against Bundibugyo virus disease. We performed a systematic review and meta-analysis of published studies of antibody cross-reactivity to Bundibugyo virus (BDBV) after vaccination with previously approved Ebola vaccines (Ervebo or Zabdeno/Mvabea). We find on average a 2.8-fold (95% predictive interval, PI: 2.6-3.0) drop in binding (n = 8 observations from 4 studies) and 3.1-fold drop (95% PI: 2.0-4.8) in neutralization (n = 2 observations from 1 study) between Ebola virus and BDBV antigens after Ervebo vaccination, which appears maintained over time after vaccination. Very limited data on cross reactivity after Zabdeno/Mvabea vaccination suggests a higher drop in recognition of BDBV (39.7-fold, 95% PI: 24.8-63.8; n = 3 observations from 2 studies). In addition to analysis of antibody recognition in humans, we also investigated evidence for vaccine protection from BDBV challenge in animal models after Ervebo or other recombinant vesicular stomatitis virus (rVSV) based vaccines containing only Ebola antigen. A single study in NHP showed non-significant vaccine protection from BDBV challenge, while a study in ferrets showed significant protection after both one and two doses. The available data demonstrate immune cross-reactivity and some evidence for protection in animals, although further clinical and pre-clinical data is urgently needed to inform decisions on the use of Ervebo to protect against Bundibugyo virus disease.