The Ebola virus is responsible for severe hemorrhagic fevers with a mortality rate of 50% to 90%. Vaccine development requires a good understanding of the characteristics of the interaction between the virus and the immune system. To fight an infection, the immune system has several strings to its bow. First, an innate response, which is not sufficient in the case of Ebola. Then there is an adaptive immune response. It activates B cells, which create antibodies to certain proteins in the virus, the antigens, and T cells, which learn to recognize the antigens directly. CEA-Joliot researchers, in collaboration with Genopole partners Excellgene and Vaxeal holding SA (Switzerland), investigated the immune responses of organisms that defeated Ebola disease.  

 High levels of antibodies directed against the GP protein, an Ebola virus antigen, were found in patients recovering from infection. CD8 and CD4 T cell responses also appear to be involved in the control of Ebola infection in animals, and CD4 T cells are necessary to induce resistance to the virus. Apart from the response to the GP protein, strong T cell responses to a viral capsid nucleoprotein (NP) are observed in animal models, which protect against infection. In convalescent Ebola patients, most of the T-cell responses developed against the virus were found to target NP. However, very few T cell recognition sites (epitopes) specific to both Ebola GP and NP proteins have been identified in humans.

An epitope is the part of the virus antigen that can be recognized by T cells. It is therefore the gateway for T cells to attack Ebola. In order to map and characterize CD4 T cell responses to the GP and NP antigens, the researchers have established a large-scale approach to identify epitopes in healthy donors. The originality of the approach is to use cells collected from people who have never been in contact with the virus. The study was also conducted outside of any infectious context in the donors. The T lymphocytes collected were used to generate specific T cell lines, stimulated by GP and NP peptides derived from the Ebola-Zaire virus. 27 NP peptides and 33 GP peptides were selected. The specificity of CD4 T lymphocytes in response to the peptides was analyzed. The researchers thus identified 17 epitopes derived from Ebola Zaire NP and GP proteins, summarizing approximately half the magnitude of the T cell response and generating a T cell response in all donors tested. These epitopes therefore appear to be the most important CD4 T cell epitopes for the Ebola response.

Considering that current vaccine candidates contain only components of the GP protein, the results of this study reveal several epitopes derived from the NP protein, making the latter appear to be a relevant target for inducing a strong CD4 T cell response to Ebola. The authors suggest that components of the NP protein could be included in the design of new Ebola vaccines. In addition, the approach used here would allow anticipation of the T-cell response prior to infection, which is valuable information at the time of emerging epidemics such as SARS-COV-2.