Oral immunization with recombinant hepatitis E virus antigen displayed on the Lactococcus lactis surface enhances ORF2-specific mucosal and systemic immune responses in mice

• HEV ORF2 antigen was displayed by the recombinant L. lactis utilizing an ice nucleation protein (INP)-based anchor system.
• Oral immunization mice with the recombinant L. lactis can elicit comprehensive mucosal (IgA) immune responses.
• The recombinant L. lactis can enhance splenocyte proliferation and Th2-grouped cytokines secretion in vitro.
• The obtained immune properties of the recombinant L. lactis would highlight the later investigation on HEV oral vaccine.

Hepatitis E virus (HEV) as a recognized zoonotic pathogen has posed global burden on public health, which is exacerbated by lack of efficient vaccine. In this study, we constructed a recombinant (inaQ-ORF2 gene fusion) Lactococcus lactis (L. lactis) strain NZ3900 that expresses and displays the hepatitis E virus antigen ORF2 utilizing an ice uncleation protein-based anchor system. After oral vaccination of BALB/c mice, significantly higher levels of ORF2-specific mucosal IgA and serum IgG were detected and cellular immunity was also induced. These findings further support that L. lactis-based HEV antigen vaccines could be used for human and animal protection against infection.