Human papillomaviruses (HPV) are present in approximately 95% of all cervical carcinomas and the HPV E6 and E7 genes are continuously expressed in these lesions. There is also circumstantial evidence that often natural immunity against HPV is generated and that this is of influence on HPV-induced lesions. Stimulation of the immune system by proper presentation of relevant HPV antigens might, therefore, lead to a prophylactic or therapeutic immunological intervention for HPV-induced lesions. For this purpose we have expressed the E6 and E7 protein of HPV 16 in an attenuated strain of Salmonella typhimurium (SL3261, aroA mutation), which has been used extensively as a live vector. Live recombinant Salmonella vaccines have the ability to elicit humoral, secretory and cell-mediated immune responses, including cytotoxic T cells, against the heterologous antigens they express. This report describes the construction of recombinant Salmonella strains expressing the HPV 16 E6 and E7 proteins, and the induction of an HPV-16-specific immune response in mice after immunization with these live vectors.
Key words Human papilloma virus Cancer Vaccine Salmonella typhimurium
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1.European Cancer Centre, c/o AZVU, P.O.Box 7057, 1007 MB, Amsterdam, The Netherlands, Fax + 31 + 20 + 6444551, E-mail ecc@euronet.nlThe Netherlands
2.University of St. Andrews, Department of Biochemistry and Microbiology, Irving Building, North Street, St. Andrews, ScotlandUK
3.Laboratory of Virology, National Institute of Public Health and Environmental Protection, P.O. Box 1, 3720 BA Bilthoven, The NetherlandsThe Netherlands
4.Laboratory of Pathology, National Institute of Public Health and Environmental Protection, P.O. Box 1, 3720 BA Bilthoven, The NetherlandsThe Netherlands
5.Unit of Molecular Microbiology, National Institute of Public Health and Environmental Protection, P.O. Box 1, 3720 BA Bilthoven, The NetherlandsThe Netherlands
6.Department of Functional Morphology, Faculty of Veterinary Medicine, PO Box 80.157, 3508 TD Utrecht, The NetherlandsThe Netherlands