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

To investigate specific immune responses elicited by a recombinant Listeria monocytogenes strain LM4 deltahly::E7 and assess protective effect in C57BL/6 mice.

C57BL/6 mice were intraperitoneally immunized with LM4 deltahly:: 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.

The immune responses elicited by LM4 deltahly::E7 were biased towards Th1 type in the ELISPOT assay. Also, LM4 deltahly::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 delta hly::E7 was 1:400 in the ELISA assay. Furthermore, immunization with LM deltahly::E7 protected all mice against the lethal tumor cell challenge.

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.