Ebola hemorrhagic fever is a scary disease. Not only a scary disease to contract and experience, but also a scary disease to survive: news this week has covered the deteriorating condition of the Scottish nurse who survived acute Ebola infection in 2014. Stories of survivors with sudden onset of complications have highlighted how little we know about this disease and those who survive it.
The epidemic – slowing but not over – also highlighted our need for better antiviral therapy for this terrible disease. The Zmapp antibody combination showed promise, but it’s hard to separate the Zmapp treatment from the improved quality of care that those who received this treatment also had.
The Ebola virus of the 2014-2015* outbreak is one of four disease-causing Ebola viruses so far discovered: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV), and Bundibugyo ebolavirus (BDBV). The fifth, Reston ebolavirus (RESTV), did not cause disease in exposed lab workers. Most outbreaks have been caused by the Zaire and Sudan ebolaviruses.
Most monoclonal antibody treatments have focused on a single Ebola virus species, meaning they would only be effective in an outbreak of the same species. Two articles published this week in the Journal of Virology aim to make a cross-protective antibody treatment for both viral species. Researchers from government, academia, and industry collaborated to produce pan-Ebola protective antibodies that could be used no matter the outbreak species.
In one article, the scientists describe macaque antibodies against a mixture of glycoproteins from ZEBOV, SUDV, and Marburg virus (MARV), another filovirus that causes outbreaks of hemorrhagic fever. The GP1 glycoprotein is a good candidate due to identical amino acid sequences in ZEBOV and SUDV (65%) and between ebolavirus and MARV (30%). One of the antibodies bound the core GP1 of all ebolavirus species, neutralizing VLPs containing GP1 from all three viruses. This antibody also rescued all mice when administered immediately after infection; delaying treatment rescued only 40% of the mice (but without any treatment, all mice succumbed to their infection). Inspired by Zmapp, the scientists also found that combined antibody cocktails rescued infected mice.
In the second article, mice were used to generate antibodies, which were also made against the GP1 glycoprotein. The scientists identified four antibodies with broadly neutralizing activity, including one that protected mice against both SUDV and ZEBOV infection. This is the first antibody described with protective effects against more than one ebolavirus species. These researchers also showed that the Fc portion of the antibody (the part that doesn’t directly bind the virus) plays a role in protecting against the virus – meaning an antibody is more likely to be effective than a peptide that binds to the GP1 and blocks viral attachment or fusion.
What comes next for these studies? If nonhuman primate studies go well, this introduces the possibility of broadly protective filovirus treatment. And while no treatment is guaranteed to eliminate the post-Ebola symptoms that have been appearing (see the well-written Virology Down Under blog for more), these cross-reactive antibodies may be a step forward toward treating future outbreaks quickly. With recent highlights of neglected tropical diseases, it’s clear that one effective treatment can have a big difference in a large number of human lives.
*I recognize this is wishful typing, but I refuse to write 2014-??
-- Julie Wolf