A novel mucosal vaccine based on live Lactococci expressing E7 antigen and IL-12 induces systemic and mucosal immune responses and protects mice against human papillomavirus type 16-induced tumors.
Current strategies to prevent or treat human papillomavirus type 16 (HPV-16) infection are promising, but remain costly. More economical but efficient vaccines are thus needed. In this study, we evaluated the protective effects of mucosally coadministered live Lactococcus lactis strains expressing cell wall-anchored E7 Ag and a secreted form of IL-12 to treat HPV-16-induced tumors in a murine model. When challenged with lethal levels of tumor cell line TC-1 expressing E7, immunized mice showed full prevention of TC-1-induced tumors, even after a second challenge, suggesting that this prophylactic immunization can provide long-lasting immunity. Therapeutic immunization with L. lactis recombinant strains, i.e., 7 days after TC-1 injection, induced regression of palpable tumors in treated mice. The antitumor effects of vaccination occurred through a CTL response, which is CD4+ and CD8+ dependent. Furthermore, immunized mice developed an E7-specific mucosal immune response. These preclinical results suggest the feasibility of the low-cost mucosal vaccination and/or immunotherapy strategies against HPV-related cervical cancer in humans.
Bermúdez-Humarán
Luis G
LG
Unité de Recherches Laitières et de Génétique Appliquée, Institut National de la Recherche Agronomique, Domaine de Vilvert, Jouy-en-Josas, France.
Cortes-Perez
Naima G
NG
Lefèvre
François
F
Guimarães
Valeria
V
Rabot
Sylvie
S
Alcocer-Gonzalez
Juan M
JM
Gratadoux
Jean-Jacques
JJ
Rodriguez-Padilla
Cristina
C
Tamez-Guerra
Reyes S
RS
Corthier
Gérard
G
Gruss
Alexandra
A
Langella
Philippe
P
D000281:Administration, Intranasal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D004195:Disease Models, Animal; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D013294:Lactococcus lactis / Q000235:genetics / Q000276:immunology; D051379:Mice; D009297:Nasal Mucosa / Q000276:immunology; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000517:prevention & control* / Q000628:therapy; D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D014765:Viral Vaccines / Q000008:administration & dosage
D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16; D018664:Interleukin-12