Protective immune responses induced by a recombinant Listeria monocytogenes delivering HPV16 E7

Abstract:

Abstract:［Objective］To investigate specific immune responses elicited by a recombinant Listeria monocytogenes strain LM4△hly:: E7 and assess protective effect in C57BL/6 mice.［Methods］ C57BL/6 mice were intraperitoneally immunized with LM4△hly::E7 at 1-week intervals．After the second immunization，cellular immunity elicited by this recombinant L．monocytogenes strain was analyzed via an ELISPOT assay，Cytotoxic T lymphocytes (CTL) measurement assay and analysis of effector T cells proportion in the splenocytes．Also，the serum antibodies against HPV16 E7 protein were determined in an ELISA assay．Finally，protective effect was assessed against the challenge with TC-1 tumor cells.［Results］The immune responses elicited by LM4△hly::E7 were biased towards Th1 type in the ELISPOT assay．Also，LM4△hly::E7 was able to induce E7-specific CTL activity，with average specific lysis of 72%，which was highly significant difference compared with the controls (P＜0.01)．Moreover，the proportion of effector T cells in the spleens were increased in mice immunized with recombinant L．monocytogenes strain (P＜0.05). The titer of E7-specific antibodies in mice immunized with LM4△hly::E7 was 1:400 in the ELISA assay． Furthermore，immunization with LM △hly::E7 protected all mice against the lethal tumor cell challenge．［Conclusion］ The data suggest that attenuated Listeria monocytogenes delivering HPV16 E7 antigen could induce both E7-specific cell mediated immunity and humoral immunity，and had a protective effect against challenge with TC-1 tumor cells.