Journal
JOURNAL OF MEDICAL VIROLOGY
Volume 91, Issue 2, Pages 296-307Publisher
WILEY
DOI: 10.1002/jmv.25303
Keywords
enzyme-linked immunospot (ELISPOT); human papillomavirus type 16 (HPV-16); Lactococcus lactis; oral immunization; pNZ8123; vaccine
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Funding
- Keyvan Virology Specialty Laboratory (KVSL)
- Islamic Azad University, Science and Research Branch (SRBIAU) (Tehran, Iran)
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The ORFs of both native and codon-optimized E7 genes were successfully fused to SPusp45 signal peptide and expressed by a nisin-controlled gene expression system in the NZ9000 strains of Lactococcus lactis. Recombinant strains were confirmed by Western blot analysis. To measure immune responses against the E7 antigen, specific-pathogen-free C57BL/6 mice were inoculated with L lactis harboring pNZ8123-rE7 by oral gavage. Then, specific antibodies and cytokines were measured by enzyme-linked immunosorbent assay and enzyme-linked immunospot assay, respectively. Oral administration of L lactis strains expressing rE7 elicited the highest levels of E7-specific antibody and greatest numbers of E7-specific CD4(+) T helper and CD8(+) T cell precursors. Our outcomes indicated that the HPV-16 E7 specific IL-2- and IFN-gamma-secreting T cells in antigen-stimulated splenocytes and intestinal mucosal lymphocytes were significantly higher than the control groups. Our data also demonstrated that mice vaccinated with recombinant L lactis were able to generate potent protective effects against challenge with the E7-expressing tumor cell line (TC-1). Moreover, L lactis containing pNZ8123-HPV16-optiE7 showed strong therapeutic antitumor effects against established tumors in vivo. These findings demonstrate that recombinant L lactis induce both humoral and cellular immune responses in mice and are therefore recommended for therapeutic treatments in humans after oral administration.
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