YY1 Activates WSSV Promoter for Enhanced Vaccine Production and Efficacy.

The baculovirus expression vector system (BEVS) has been used as a preferred platform for the production of recombinant protein complexes and efficacious vaccines. However, limited protein yield hinders the application of BEVS. It is well accepted that transcription enhancers are capable of increasing translational efficiency of mRNAs, thereby achieving better protein production. In this study, the ability of YY1 as a transcription enhancer was assessed. YY1 could interact with the WSSV promoter via binding to special DNA sites in BEVS. The effects of YY1 on protein expression mediated by WSSV promoter of BEVS was investigated using eGFP as a reporter gene. Enhanced eGFP expression was observed in Sf-9 cells with YY1. On this basis, a modified vector combining promoter and YY1 was developed to express either secreting CSFV E2 or baculovirus surface displayed H5 HA of AIVs. Compared to control groups without YY1, E2 protein yield increases to 1.6-fold, while H5 production improves as revealed by an upregulated hemagglutination titer of 8-fold at least. Moreover, with YY1, H5 displaying baculovirus driven by WSSV promoter (BV-YY1--HA) sustains the transduction activity in CEF cells. In chicken, BV-YY1--HA elicits a robust immune response against H5 AIVs in the absence of adjuvant, as indicated by specific antibody and cytokine responses. The findings suggest its potential function as both a vectored and subunit vaccine. These results demonstrate that the coexpression with YY1 serves as a promising strategy to extensively improve the efficiency of BEVS for efficacious vaccine production.