title: An inducible surface presentation system improves cellular immunity against human papillomavirus type 16 E7 antigen in mice after nasal administration with recombinant lactococci.
abstract: Human papillomavirus type 16 (HPV-16) is the major causative agent of cervical cancer. To date, vaccine strategies against HPV-16 are based on the ability of the E7 oncoprotein to elicit an immune response against this virus. In this study, the use of an inducible or a constitutive system to produce the HPV-16 E7 protein in Lactococcus lactis, a non-pathogenic and non-invasive Gram-positive bacterium, was compared. The highest E7 production was obtained with the inducible system. When mice were immunized intranasally with recombinant lactococci expressing either inducible or constitutive E7, an antigen-specific cellular response (i.e. secretion of IL2 and IFN-gamma cytokines) was evoked and was substantially higher in mice receiving L. lactis expressing E7 with the inducible system. As bacterial antigen location may influence the immune response, recombinant L. lactis strains that produced E7 in three cellular locations, intracellular, secreted or cell-wall-anchored were evaluated. The highest immune response was elicited by administration of L. lactis producing an inducible cell-wall-anchored form of E7 protein. These promising results represent a step towards the development of a new, safe mucosal vector to treat HPV-related cervical cancer.
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas. Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L., Mexico 2Unité de Recherches Laitières et de Génétique Appliquée, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Bermúdez-Humarán
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas. Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L., Mexico 2Unité de Recherches Laitières et de Génétique Appliquée, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France.
authors.forename: Naima G
authors.initials: NG
authors.lastname: Cortes-Perez
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas. Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L., Mexico 2Unité de Recherches Laitières et de Génétique Appliquée, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Loir
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas. Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L., Mexico 2Unité de Recherches Laitières et de Génétique Appliquée, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Alcocer-González
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas. Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L., Mexico 2Unité de Recherches Laitières et de Génétique Appliquée, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France.
authors.forename: Reyes S
authors.initials: RS
authors.lastname: Tamez-Guerra
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas. Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L., Mexico 2Unité de Recherches Laitières et de Génétique Appliquée, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France.
authors.forename: Roberto Montes
authors.initials: RM
authors.lastname: de Oca-Luna
authors.affiliation: Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas. Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L., Mexico 2Unité de Recherches Laitières et de Génétique Appliquée, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002473:Cell Wall / Q000378:metabolism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D013294:Lactococcus lactis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D007376:Interleukin-2; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma