Dengue vaccine development is considered a global public health priority， but the antibody-dependent enhancement (ADE) issues have critically restricted vaccine development. Recent findings have demonstrated that pre-membrane (prM) protein was involved in dengue virus (DENV) infection enhancement. Although the importance of prM antibodies have been well characterized， only a few epitopes in DENV prM protein have ever been identified. In this study， we screened five potential linear epitopes located at positions pr1 (1-16aa)， pr3 (13-28aa)， pr4 (19-34aa)， pr9 (49-64aa)， and pr10 (55-70aa) in pr protein using peptide scanning and comprehensive bioinformatics analysis. Then， we found that only pr4 ... More
Dengue vaccine development is considered a global public health priority， but the antibody-dependent enhancement (ADE) issues have critically restricted vaccine development. Recent findings have demonstrated that pre-membrane (prM) protein was involved in dengue virus (DENV) infection enhancement. Although the importance of prM antibodies have been well characterized， only a few epitopes in DENV prM protein have ever been identified. In this study， we screened five potential linear epitopes located at positions pr1 (1-16aa)， pr3 (13-28aa)， pr4 (19-34aa)， pr9 (49-64aa)， and pr10 (55-70aa) in pr protein using peptide scanning and comprehensive bioinformatics analysis. Then， we found that only pr4 (19-34aa) could elicit high-titer antibodies in Balb/c mice， and this epitope could react with sera from DENV2-infected patients， suggesting that specific antibodies against epitope peptide pr4 were elicited in both DENV-infected mice and human. In addition， our data demonstrated that anti-pr4 sera showed limited neutralizing activity but significant ADE activity toward standard DENV serotypes and imDENV. Hence， it seems responsible to hypothesize that anti-pr4 serum was infection-enhancing antibody and pr4 was infection-enhancing epitope. In conclusion， we characterized a novel infection-enhancing epitope on dengue pr protein， a finding that may provide new insight into the pathogenesis of DENV infection and contribute to dengue vaccine design.
