Recombinant AcHERV-baculovirus vaccine elicits robust immune responses against human norovirus.

Human norovirus (HuNoV) is a leading global cause of acute viral gastroenteritis, placing a particularly high burden on pediatric and elderly populations. Despite significant progress in HuNoV vaccine development, including advanced clinical trials of virus-like particle (VLP)-based candidates, no vaccine has received regulatory approval to date. In this study, we developed a recombinant baculovirus-based vaccine, AcHERV-HuNoV, designed to express the human norovirus (HuNoV) VP1 protein. This vaccine utilizes the AcHERV platform, which consists of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) with the human endogenous retrovirus (HERV) envelope protein to enhance delivery efficiency. The AcHERV-HuNoV vaccine incorporates HERV-W-derived Syncytin-1 on the baculovirus envelope and the VP1 gene from either the GII.4 or GII.17 genotype to represent prevalent strains in Korea. This system enhances gene delivery to mammalian cells while preventing in vivo replication. Norovirus VLPs were produced and purified from insect cells to serve as control vaccines and comparative antigens. Immunogenicity was evaluated in BALB/c mice following intramuscular and intranasal administration of AcHERV-HuNoV. The vaccine induced robust immune responses, with serum IgG geometric mean titers (GMTs) reaching 14,132 (95% CI: 9080-21,979) and IgA levels of 262 (95% CI: 70-982) specific for GII.4 after final immunization, as well as potent surrogate neutralizing activity determined by the porcine gastric mucin (PGM)-blocking assay. Furthermore, it induced robust cellular immunity characterized by increased production of Th1, Th2, and Th17 cytokines. These results demonstrate the promising potential of AcHERV-HuNoV as a genetic vaccine candidate capable of inducing both humoral and cellular immune responses against HuNoV infection.