ORALLY ADMINISTERED HPV 16 VACCINE STIMULATING GUT-ASSOCIATED LYMPHOID TISSUES

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Human papillomavirus type16 (HPV16) is the most important risk factor for cervical cancer. Thus, effective prophylactic vaccine against HPV 16 is expected for prevention of cervical cancer development, which is the secondary common cancer of women worldwide.Recent study showed that nasal administration of HPV16 virus-like particles (VLP) is able to elicit mucosal antibody neutralizing HPV 16. In the present study, we tested an efficacy of orally administered HPV16 vaccine using yeast synthesizing HPV 16 VLP (HPV 16 VLP-yeast). Preliminary experiments showed that freeze dried yeast was good candidate for delivering antigen to the gut and stimulating the gut-associated lymphoid tissues (GALT), since it was not digested in the stomach but digested in the intestine.Positive control mice were nasally administered with purified HPV16 VLP (Nasal-Ad), and the others were orally administered with freeze dried yeast (Oral-Ad). Two mice were orally administered with control yeast, two mice with HPV6 VLP-yeast, 6 mice with HPv16 VLP-yeast, and 12 mice with HPV16 VLP-yeast and Cholera toxin (CT). HPV-specific antibody responses were tested with HPV6- and 16-VLP-ELISA. Two Nasal-Ad mice, 3 of 6 Oral-Ad mice with HPV16 VLP-yeast, and 4 of 12 Oral-Ad mice with HPV 16 VLP-yeast + CT elicited HPV 16-specific IgA and IgG serum antibody (Ab), whereas mice administered with control yeast or with HPV6-VLP-yeast had no such responses.The liters of the serum Ab were as high as those in the mice nasally administered with HPV16 VLP, and no difference in serum Ab titers was observed by administrating CT or not. Weak but HPV 16-specifc IgA responses were detected in vaginal secretions of 2 of 12 Oral-Ad mice with CT. Now we are optimizing the condition able to induce stronger mucosal IgA response.