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An inducible surface presentation system improves cellular immunity against human papillomavirus type 16 E7 antigen in mice after nasal administration with recombinant lactococci

Luis G. Bermúdez-Humarán^1,2, Naima G. Cortes-Perez^1,2, Yves Le Loir², Juan M. Alcocer-González¹, Reyes S. Tamez-Guerra¹, Roberto Montes de Oca-Luna¹ and Philippe Langella²

¹Laboratorio 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

Correspondence Philippe Langella langella{at}jouy.inra.fr

Received September 13, 2003
Accepted January 7, 2004

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- 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.

Abbreviations: CxCa, cervical cancer; HPV-16, human papillomavirus type 16; LAB, lactic acid bacteria.

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