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Vaccination with the Ebola Zaire vaccine (rVSVΔG-ZEBOV-GP; Ervebo) was associated with a significantly lower risk of death in patients with confirmed Ebola disease, even for those vaccinated shortly after exposure to the virus, a retrospective analysis found.

Among patients admitted to Ebola health facilities in the Democratic Republic of the Congo, the unadjusted case fatality rate (CFR) was 25.1% for vaccinated patients compared with 56.2% for unvaccinated patients (P<0.0001), Rebecca Coulborn, MPH, of Epicentre in Paris, and colleagues reported in .

In an adjusted analysis, protection against death increased as time elapsed from vaccination to symptom onset. However, even vaccination shortly before symptom onset was tied to a reduced risk of death compared with being unvaccinated:

• 27% vaccinated less than 2 days before symptom onset died (adjusted relative risk [aRR] 0.56, 95% CI 0.36-0.82, P=0.0046)
• 20% vaccinated 3-9 days before symptom onset died (aRR 0.44, 95% CI 0.29-0.65, P=0.0001)
• 18% vaccinated 10 or more days before symptom onset died (aRR 0.40, 95% CI 0.21-0.69, P=0.0022)

"Our evidence reinforces the importance of vaccinating populations who are at risk of exposure to Ebola virus as early as possible during outbreaks to reduce the risk of infection and severe complications of Ebola virus disease, including death," the authors wrote.

"Late vaccination (i.e., after Ebola virus disease exposure, even when administered shortly before symptom onset) was significantly protective against death," they emphasized.

When looking at Ebola virus disease-specific treatments and interactions with the vaccine, they found that treatment with the monoclonal antibody mAB114 and the monoclonal combination REGN-EB3 substantially reduced risk of death among patients with confirmed Ebola disease, regardless of vaccination status.

Overall, mAB114 reduced the risk of death by 56% (aRR 0.44, 95% CI 0.33-0.57, P<0.0001) and REGN-EB3 reduced the risk by 60% (aRR 0.40, 95% CI 0.30-0.52, P<0.0001). Also, no negative effects of the vaccine on Ebola treatment were noted -- among patients who were vaccinated shortly before starting treatment, those treated with mAB114 or REGN-EB3 had a 71% decreased risk of dying (aRR 0.29, 95% CI 0.02-1.31, P=0.22) compared with those who were not vaccinated and treated.

"As with Ebola therapeutics, timing matters," wrote William Fischer II, MD, and David Wohl, MD, of the University of North Carolina at Chapel Hill, in an . "Importantly the greatest reduction in mortality occurred among those who were both vaccinated and received a therapeutic," a finding that was also reported in the 2019 PALM study, they pointed out, "suggesting a potential additive effect of vaccination and treatment."

Of note, Coulborn and colleagues identified a potential mechanism for why the vaccine had such a profound effect on mortality. Vaccinated patients had significantly higher cycle threshold values for nucleoprotein -- an indicator of lower viremia -- than unvaccinated patients, indicating that the vaccine induced a protective immune response. In fact, those who were vaccinated 21 days or longer before symptom onset had the highest difference in cycle threshold values compared with unvaccinated patients (median 30 vs 21.4 cycles).

"A bundled approach to care including vaccination before the outbreak coupled with early diagnostics, optimized supportive care, and treatment with effective antiviral therapeutics can turn the tide against this disease," Fischer and Wohl wrote. "Now that high rates of mortality due to Ebola virus are no longer a given, acceptance of these life-saving measures can be cultivated, but only if they are quickly deployed where and when they are needed."

The retrospective cohort analysis looked at data from 2,279 patients with confirmed Ebola disease who were admitted to Ebola health facilities in the Democratic Republic of the Congo between July 27, 2018 to April 27, 2020.

Of these, 45% were not vaccinated for Ebola and 37% had unknown vaccination status. Four percent were vaccinated 2 days or less before symptom onset, 6% were vaccinated 3-9 days before symptom onset, 3% were vaccinated 10 days or more before symptom onset, and 2% were vaccinated 21 days or more before symptom onset. Most vaccinated patients were 15-59 years of age.

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