The ongoing Bundibugyo ebolavirus (BDBV) outbreak in the Democratic Republic of the Congo is the second-largest Ebolavirus outbreak globally, with more than 6,000 confirmed cases and a mortality rate of 48 percent. Currently, no licensed BDBV vaccine is available. The VSV-EBOV vaccine, developed against the related Ebola virus (EBOV) and licensed under the name Ervebo, has shown partial cross-protection against BDBV in non-human primates and induces BDBV-reactive antibodies in vaccinated individuals. However, the extent and potential protective role of this cross-reactivity in humans remain unclear. Now, a study led by researchers of the German Center for Infection Research (DZIF) and published in The Lancet Infectious Diseases shows that a single immunization with the licensed EBOV vaccine can induce T cell responses that recognize BDBV.
T-cell responses contribute to viral control and protection against severe disease for diverse types of viruses. Because T cells can recognize conserved viral epitopes, they may potentially cross-react between related viruses. However, whether VSV-EBOV vaccination also induces T cells that recognize BDBV in humans has remained unknown.
A DZIF research team led by Dr. Leonie Mayer and Prof. Marylyn Addo from the Institute for Infection Research and Vaccine Development at the University Medical Center Hamburg-Eppendorf and Prof. Christof Geldmacher and Dr. Rolanda Londt from the Institute of Infectious Diseases and Tropical Medicine at the LMU University Hospital Munich therefore analyzed and mapped T-cell responses against EBOV, BDBV and Sudan virus (SUDV) in VSV-EBOV-vaccinated individuals. The glycoproteins of the three viruses are phylogenetically distant, with EBOV and BDBV sharing 66.3 percent amino acid identity, compared with 56.3 percent between EBOV and SUDV.
“Using multiple sequence alignments—the parallel comparison of multiple amino acid sequences—we identified several sequences that are highly conserved among the glycoproteins of EBOV, BDBV, and SUDV, and tested these regions for their interactions with the immune systems of vaccine recipients,” says first author Mayer. The researchers then assessed cross-reactive T cell responses in 20 vaccine recipients at day 28 after VSV-EBOV vaccination. Of these vaccine recipients, 16 showed EBOV-glycoprotein-specific T cell responses, 13 showed BDBV-glycoprotein-reactive T cell responses and seven showed SUDV-glycoprotein-reactive T cell responses at day 28 after vaccination. Most vaccinees with a positive EBOV-glycoprotein response also had BDBV-reactive T cells.
The study demonstrates that a single immunization with the available, licensed EBOV vaccine can induce T cell cross-reactivity against BDBV and—to a lesser extent—against SUDV. While it is not known, whether these T cells can contribute to improved clinical outcomes upon infection with BDBV, preclinical studies in non-human primates suggest that T cell responses are required for vaccine-mediated protection.
“Our findings provide the first evidence that VSV-EBOV vaccination against ebolavirus induces BDBV-cross-reactive T cell responses,” says Geldmacher. “While the study has limitations due to its small sample size, in the absence of a BDBV-specific vaccine, the study supports the systematic evaluation of the EBOV vaccine within clinical trials during the current BDBV outbreak,” he concludes.
This study was supported by the DZIF, the European Vaccines Hub for Pandemic Readiness (EVH), and the DFG-funded Collaborative Research Center 1648 “Emerging Viruses: Pathogenesis, Structure, Immunity”.
The Lancet Infectious Diseases
Experimental study
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