Prophylactic and therapeutic efficacy of an attenuated Listeria monocytogenes-based vaccine delivering HPV16 E7 in a mouse model
International Journal of Molecular Medicine
Listeria monocytogenes (L. monocytogenes) has been developed as a cancer vaccine vector due to its ability to elicit strong innate and adaptive immune responses. For clinical application, it is necessary to exploit a Listeria platform strain that is safe and that also retains its immunogenicity to develop vaccine candidates against cancer. In this study, a highly attenuated strain with a deletion of actA/plcB was employed as a vector to deliver the human papillomavirus type 16 (HPV16) E7
... 6 (HPV16) E7 antigen, which was stably inserted into the chromosome of L. monocytogenes. The prophylactic and therapeutic efficacy of the recombinant L. monocytogenes strain expressing E7 (LM1-2-E7) were evaluated in C57BL/6 mice. In prophylactic tumor challenge assays, immunization with the recombinant strain LM1-2-E7 was able to protect against tumor formation in 87.5% of the mice, even after a second challenge, suggesting that this prophylactic immunization can provide long-lasting immunity. In the therapeutic setting, immunization with LM1-2-E7 led to tumor regression in 50% of the mice and suppressed tumor growth in the remaining mice. The results showed that the recombinant strain was cleared by the immune system within 5 days after immunization and induced a Th1 immune response against E7 peptide and E7-specific cytotoxic T-lymphocyte (CTL) killing activity without severe inflammatory responses in the spleen and liver. Markedly, recombinant Listeria strain resulted in preferential accumulation within tumor tissues and induced higher numbers of CD8 + T cells that infiltrated into the tumor, which were associated with retardation of tumor growth. Collectively, these data indicate that LM1-2-E7 is a possible vaccine candidate against cervical cancer.