Abstract
A dramatic increase in incidents has been documented indicating that DENV has become a major international health concern. E protein domain III (EDIII) is the receptor binding domain, and was demonstrated that EDIII contains serotype-specific epitopes. In this study, the E.coli-based fusion protein, containing a TLR5 agonist, flagellin (FliC), and EDIII epitopes in a single polypeptide, which could elicit significantly higher neutralizing antibodies than EDIII mixed with FliC. We further evaluated the heterologous prime-boost strategy using adenovirus vector encoding prME and FliC-EDIII fusion protein in BALB/c mice. We found anti-EDIII specific antibodies were the dominant neutralizing ability, while heterologous prime-boost strategy elicited significantly higher anti-EDIII total IgG titer compared with homologous prime-boost immunization. Moreover, the neutralizing ability against all serotypes of DENV was observed in tetravalent Ad-prME prime/FliC-EDIII boost regimen. These result demonstrated the feasibility of developing DENV vaccine using heterologous prime-boost strategy.