Identifying an immunodominant epitope of dengue non-structural protein 1 (NS1) in acute secondary dengue infections for vaccine development or development of treatment modalities
Ramu ST., Ariyaratne D., Jeewandara C., Jayathilaka D., Gomes L., Wijewickrama A., Ogg G., Malavige GN.
Dengue infection is a rapidly emerging disease with no licensed treatment or vaccine available. It is currently unclear whether antibody responses to dengue virus (DENV) NS1 are associated with protection or pathogenesis. To further evaluate, we sought to identify an immunodominant epitope of NS1 of DENV2 in patients to identify epitopes for effective vaccine development or for production of monoclonal antibodies. An in-house ELISA was used to detect immunodominant epitopes of DENV2 NS1, using overlapping peptides in the serum of patients with acute secondary DENV2 infection, resulting in dengue fever (DF = 20) or dengue haemorrhagic fever (DHF = 20) and in healthy individuals (n = 11). Responses to the recombinant C-terminal region were assessed. The region corresponding to 289 to 313aa (distal C-terminal region) was found to be the most immunodominant region in all patients, irrespective of disease severity. However, 5/9 DENV seronegative individuals also had high levels of antibodies to the linear peptides representing this region but they had a significantly lower response to the recombinant C-terminal protein. The 289-313aa region was found to be highly conserved between the four DENV serotypes and other flaviviruses. As the distal C-terminal region of DENV2 NS1 protein appears to be highly immunogenic and highly conserved, it would be important to target this region in development of DENV vaccines or for production of therapeutic monoclonal antibodies.