Emory and CDC scientists discover strong immune response to Ebola virus

A group of scientists from Emory University and the Centers for Disease Control and Prevention (CDC) has discovered that a mouse strain of Ebola virus, adapted from a human strain, induces a strong T-cell immune response, despite the belief of some scientists that the lethal effects of Ebola are due to virus-caused suppression of the immune system. This new information about the immune response to Ebola could be an important step in developing an effective vaccine against the disease.

Ebola is an RNA virus that causes a severe hemorrhagic fever in humans and non-human primates, beginning within a few days of infection, with mortality of 50 to 80% in as little as one week. The mouse-adapted strain tested by the Emory and CDC scientists produces 100% mortality in mice within six to eight days following intraperitoneal injection of a low dose of virus.

Using markers of T-cell activation, the Emory and CDC scientists detected a high frequency of activated CD4 and CD8 T cells in mice beginning as early as four days post infection. In addition, the scientists detected high levels of the cytokine interferon gamma in the spleen, liver and serum. Cytokines are proteins produced by T cells that prevent the growth of viruses and make cells resistant to viral infection. The researchers concluded that, despite the measurable immune response, Ebola causes its severe and rapidly fatal response in mice because the virus is so lethal that it allows no time for the immune T cells to multiply and mount an attack.

The research was conducted by Manisha Gupta, Ph.D., immunology postodoctoral fellow at Emory and CDC; Rafi Ahmed, Ph.D., Emory professor of microbiology and immunology, Georgia Research Alliance eminent scholar and director of the Emory Vaccine Research Center; and CDC scientists Siddhartha Mahanty, Ph.D. and Pierre Rollin, Ph.D.

In additional experiments, the scientists removed all CD8 T cells from a subset of mice and did not detect interferon gamma, suggesting that CD8 T cells are the major source of cytokines induced by Ebola during acute infection. Further, scientists have shown that memory CD8 T cells, in the absence of anti-Ebola antibodies, can protect against lethal Ebola virus infection. In ongoing research, the Emory and CDC scientists are working to understand the mechanism of immune protection, which will help in the design of an Ebola vaccine.