Hybrid baculovirus-mediated prolonged hemagglutinin expression and secretion in vivo enhances the vaccine efficacy

Abstract

Abstract Viral vectors expressing the major antigen hemagglutinin (HA) are a promising vaccine platform against avian influenza virus (AIV) which poses serious threat to the poultry industry and human health. However, vector vaccines typically express HA transiently within the cells. Conversely, nanoparticles encapsulating and releasing antigens slowly in vivo potentiate humoral and cellular immune responses, hence underscoring the benefits of long-term antigen release for potent vaccine efficacy. Baculovirus (BV) is a non-pathogenic insect virus capable of transducing mammalian and avian cells and holds promise as a vaccine vector. Here we constructed a hybrid BV (Bac-FCsHW) harboring an Frt sites-flanking gene cassette expressing a fusion HA protein composed of the HA ectodomain and a GCN4 pII peptide to facilitate trimerization. Bac-FCsHW transduction of cells enabled expression and secretion of HA trimers. Co-transduction of mammalian cells with Bac-FCsHW and Bac-FLPo expressing FLPo recombinase led to FLPo recognition of Frt sites, excision and formation of episomal DNA minicircles that encompassed the HA expression cassette. Such FLPo/Frt-mediated minicircle formation remarkably prolonged and enhanced the expression of secreted HA to at least 28 days. Intramuscular co-injection of Bac-FLPo and Bac-FCsHW into BALB/c mice significantly potentiated the humoral and cellular immune responses when compared with the control groups expressing native intracellular HA, either for a short-term or long-term. These data demonstrated that BV-mediated prolonged expression and release of HA substantiated the vaccine efficacy and implicated the potentials of the FLPo/Frt-based hybrid BV vector as a new AIV vaccine platform.