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Protective Immunodominant Zaire Ebolavirus Glycoprotein Epitope in Mice

Xiangguo Qiu, Lisa Fernando, Steven M. Jones and Judie B. Alimonti

Zaire Ebolavirus (ZEBOV) causes a highly lethal severe haemorrhagic fever in humans, for which there is currently no approved vaccine available. In this study, cytokine ELISPOT assays were used to determine the ZEBOVGP-specific cytokine profile and immunodominant T cell epitopes in VSV?G/ZEBOVGP immunized Balb/C mice. Splenocytes added to pools of overlapping peptides spanning ZEBOVGP stimulated a Th1 cytokine profile with the majority of the ZEBOVGP-specific splenocytes secreting IFN-g. The splenocytes produced the strongest IFN-g response to the immunodominant peptide HNTPVYKLDISEATQ, located in the cytopathic mucin domain of GP. The immunodominant epitope was then tested for its ability to induce a protective immune response in mice challenged with a lethal dose of mouse adapted-ZEBOV. Mice immunized with the peptide plus Freund’s adjuvant survived the challenge, and had a strong ZEBOVGP-specific T and B cell immune response. Identifying the ZEBOVGP-specific cytokine profile and immunodominant epitope will aid in determining the correlates of immune protection; allow for the development of assays to assess the efficacy of the VSV?G/ZEBOVGP vaccine in immunized individuals; and provide valuable information for the development of a subunit vaccine.