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The Journal of Immunology, 2005, 175: 7297-7302.
Copyright © 2005 by The American Association of Immunologists

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

Luis G. Bermúdez-Humarán1,*,{dagger}, Naima G. Cortes-Perez1,*,{dagger}, François Lefèvre{ddagger}, Valeria Guimarães{ddagger}, Sylvie Rabot{dagger}, Juan M. Alcocer-Gonzalez§, Jean-Jacques Gratadoux*, Cristina Rodriguez-Padilla§, Reyes S. Tamez-Guerra§, Gérard Corthier{dagger}, Alexandra Gruss* and Philippe Langella2,*,{dagger}

* Unité de Recherches Laitières et de Génétique Appliquée, {dagger} Unité d’Ecologie et de Physiologie du Système Digestif, {ddagger} Unité de Virologie et Immunologie Moléculaire, and Institut National de la Recherche Agronomique, Domaine de Vilvert, Jouy-en-Josas, France; and § Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas. Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo Leon, Mexico

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.




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