Until now, it was unclear whether the virus variant currently circulating is able to infect human cells more efficiently than earlier variants and is thus contributing to the unusual dynamics of the outbreak in DRC. It was also unclear whether authorizsed vaccines against the Zaire Ebola virus could provide at least partial protection against the Bundibugyo Ebola virus. The team of Researchers from Hamburg, Berlin, Göttingen and Hannover found no evidence that the current Bundibugyo Ebola virus variant infects human cells more efficiently than previously known variants. The virus’s entry into cells was inhibited by antibodies in the serum of individuals who had been vaccinated with the VSV-ZEBOV-GP vector vaccine. The study thus provides important evidence that an already available vaccine could protect people currently at risk from severe disease and help to combat the ongoing outbreak.
No evidence of increased infectivity in the Bundibugyo Ebola virus variant
As the Zaire Ebola virus variant, which triggered the largest Ebola epidemic to date in West Africa from 2014 to 2016, had a mutation in the envelope protein that likely facilitated entry into human cells, the researchers first investigated whether the current Bundibugyo Ebola virus variant penetrates human cells more easily than earlier variants. For their investigations, the researchers used so-called pseudoviruses – non-replicating viral particles equipped with the envelope proteins of various Ebola viruses – as well as macrophages and dendritic cells derived from human monocytes, which are the main target cells of Ebola viruses. The investigations revealed no evidence of increased infectivity in the currently circulating Bundibugyo Ebola virus variant. “The results are highly relevant, as we examined not only cell lines but also fully differentiated human macrophages and dendritic cells,” says Ulrich Kalinke, Director of the Institute for Experimental Infection Research at TWINCORE, a joint institution of Hannover Medical School and the Helmholtz Centre for Infection Research (HZI), as well as head of the department of the same name at HZI. For the study, his team conducted the isolation and differentiation of human macrophages and dendritic cells and subsequently investigated how Ebola virus pseudoparticles enter these cells.
Antibodies produced following vaccination against the Zaire Ebola virus also neutralize the current Bundibugyo Ebola virus variant
To investigate whether authorized vaccines against the Zaire Ebola virus also induce antibodies that neutralize the currently circulating Bundibugyo Ebola virus variant, the researchers mixed pseudoviruses with serum samples from vaccinated individuals who had taken part in a previous clinical trial on the immunogenicity and tolerability of the VSV-ZEBOV-GP vaccine. They then analyzed the extent to which the antibodies present inhibited the entry of the pseudoviruses into human cells. It was found that most samples contained antibodies that neutralized pseudoviruses carrying the envelope protein of the current Bundibugyo Ebola virus variant, albeit less efficiently than pseudoviruses carrying the Zaire Ebola virus envelope protein.
Further studies are needed to confirm clinical benefit during the current outbreak
“Our results show that the Bundibugyo Ebola virus variant currently circulating does not have an increased potential to infect human cells compared with earlier variants. At the same time, our data suggest that the available vaccine against the Zaire Ebola virus could potentially also help to combat the current Bundibugyo Ebola virus outbreak until specific vaccines and drugs become available,” says DPZ researcher Markus Hoffmann, head of the study and lead author. However, he adds a caveat: “Our findings now need to be confirmed in studies using infectious Bundibugyo Ebola virus. Furthermore, further investigations are required to reliably assess the clinical benefit of using Zaire Ebola virus vaccines during the current outbreak.”
