Mucosal vaccination with a recombinant Salmonella typhimurium expressing human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) or HPV16VLPs purified from insect cells inhibits the growth of HPV16-expressing tumor cells in mice

Human papillomaviruses, mainly type 16 (HPV16), are responsible for cervica l intraepithelial neoplasia, which can lead, in association with other fact ors, to cervical cancer. Both Salmonella recombinant vaccine strains assemb ling HPV16 virus-like particles (VLPs) and HPV16 VLPs purified from insect cells are able to induce HPV16 neutralizing antibodies in genital secretion s of mice after nasal immunization. Anti-HPV16-specific antibodies in cervi cal secretions of women may prevent genital infection with HPV16, although this cannot be critically evaluated in the absence of an experimental model for genital papillomavirus infection. Induction of HPV16-specific cell-med iated immunity in the genital mucosa could improve the efficacy of a vaccin e and a mucosal route of immunization might be necessary to do so. It has b een shown that systemic immunization of mice with purified HPV16 VLPs confe rs protection against an HPV16-expressing tumor cell challenge through the induction of cytotoxic T-lymphocytes. Using the same C3 tumor model, we sho w that intranasal immunization of mice with purified HPV16 VLPs in a prophy lactic setting also induces anti-tumor immunity. More interestingly, mucosa l vaccination of mice with a Salmonella recombinant strain stably expressin g HPV16 L1 VLPs also induces anti-tumor immunity in prophylactic as well as in therapeutic settings. Our data suggest that attenuated Salmonella strai ns expressing chimeric VLPs containing nonstructural viral proteins might b e a promising candidate vaccine against cervical cancer by inducing both ne utralizing antibodies and cell-mediated immunity, (C) 2001 Academic Press.