Prophylactic and therapeutic efficacy of an attenuated Listeria monocytogenes-based vaccine delivering HPV16 E7 in a mouse model

Int J Mol Med. 2012 Dec;30(6):1335-42. doi: 10.3892/ijmm.2012.1136. Epub 2012 Sep 20.


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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Female
  • Genetic Vectors
  • Human papillomavirus 16 / immunology*
  • Immunity, Cellular
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / immunology
  • Liver / pathology
  • Mice
  • Mice, Inbred C57BL
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / immunology*
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / immunology
  • Papillomavirus Vaccines / therapeutic use*
  • Spleen / pathology
  • Tumor Burden
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology


  • Cancer Vaccines
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Vaccines, Attenuated
  • oncogene protein E7, Human papillomavirus type 16