Nasal immunization of mice with human papillomavirus type 16 (HPV-16) virus-like particles or with the HPV-16 L1 gene elicits specific cytotoxic T lymphocytes in vaginal draining lymph nodes

Human papillomavirus type 16 (HPV-16) infects the genital tract and is clos ely associated with the development of cervical cancer. HPV-16 initiates in fection at the genital mucosal surface; thus, mucosal immune responses are likely to contribute to defense against HPV-16 infection. However, little i nformation is available regarding the induction of immune responses in the genital tract mucosa. In this study, we evaluated the potential of intranas ally administered papillomavirus vaccines to elicit both systemic and vagin al immune responses. HPV-16 virus-like particles (VLPs) produced by self-as sembly of L1 protein and the HPV-16 L1 gene cloned into a mammalian express ion vector were used as vaccines. Intranasally administered VLPs induced se rum immunoglobulin G (IgG) and vaginal IgA secretory antibodies. Very weak serum IgG and vaginal IgA responses were found after DNA immunization. Both splenic and vaginal lymphocytes could be activated by intranasal immunizat ion with VLPs and the HPV-16 L1 gene. Activated CD4(+) Th1-like T cells wer e shown to synthesize gamma interferon, and activated CD8(+) T cells were d emonstrated to be cytotoxic.