title: Prophylactic and therapeutic efficacy of an attenuated Listeria monocytogenes-based             vaccine delivering HPV16 E7 in a mouse model.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou,                     Jiangsu 225009, P.R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jia
authors.forename: Yuelan
authors.initials: Y
authors.lastname: Yin
authors.forename: Feifei
authors.initials: F
authors.lastname: Duan
authors.forename: Hong
authors.initials: H
authors.lastname: Fu
authors.forename: Maozhi
authors.initials: M
authors.lastname: Hu
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Pan
authors.forename: Xinan
authors.initials: X
authors.lastname: Jiao
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors; D052162:Human papillomavirus 16 / Q000276:immunology*; D007111:Immunity, Cellular; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D013154:Spleen / Q000473:pathology; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D014613:Vaccines, Attenuated; C059731:oncogene protein E7, Human papillomavirus type 16