In two papers published in Cell and Cell Host Microbe together with our collaborators at VIC, CViSB, and VHFC we describe in detail antibody responses to Ebola virus. By systematic analysis of a large set of more than 170 monoclonal antibodies to Ebola virus, we investigated which immunological features play key roles in protection against the virus. This was our first set of papers where we were exclusively involved as an ‘analysis’ lab, which was a ton of fun and a great experience.
We aimed to understand which Ebola-fighting antibodies are best – and why. The hope is that the most effective antibodies can be combined in a therapeutic “cocktail.” Unlike an Ebola vaccine, these cocktails could be given to those already infected, which is important for stopping a disease that tends to emerge unexpectedly in remote locations. These studies were the first-ever side-by-side comparison of more than a hundred antibodies against Ebola virus and other related viruses, known as filoviruses. All antibodies in the panel were donated by different labs around the world, and many had not been previously characterized in such extensive detail.
In addition to identifying links between antibody target locations and activity, VHFC researchers tested this huge pool of antibodies to reveal which antibodies “neutralized” the virus, why neutralization assays so often disagree, and whether or not neutralization in test tubes adequately predicted how well these antibodies would protect live animals from Ebola virus infection. Unexpectedly, neutralization alone was not always associated with the protective ability of an antibody. Notably, we found nine antibodies that protected mice from infection without neutralizing the virus in test tubes. These antibodies likely fight infection by interacting with an infected person’s immune system, helping orchestrate a better immune response to the virus.
From the large body of results, our lab developed a network describing how each antibody feature correlates to protection, which can serve as a guide to predict whether newly identified antibodies will have therapeutic value. The next steps will be to further test promising antibody cocktails in non-human primates, and our team will also pursue engineering of antibodies that carry signature features to better drive immune system response.