title: A human papillomavirus type 16 vaccine by oral delivery of L1 protein.
abstract: To establish an edible HPV16 vaccine, we constructed a recombinant HPV16 L1-expressing Schizosaccharomyces pombe yeast strain (HPV16L1 yeast). A preliminary study revealed that freeze-dried yeast cells could be delivered safely, and were digested in the mouse intestine. The freeze-dried HPV16 L1 yeast was administered orally as an edible vaccine, with or without the mucosal adjuvant heat-labile toxin LT (R192G), to 18 female BALB/c mice. After the third immunization, none of the mice that received the edible HPV16 vaccine showed specific antibody responses, whereas all of the positive controls that were administered intranasally with 5 microg of HPV16-virus-like particles (VLP) had serum IgG, and genital IgA and IgG that reacted with HPV16-VLP in enzyme-linked immunosorbent assays (ELISAs). When a suboptimal dose (1 microg) of HPV16-VLP was administered to all the mice, including the negative control mice, 50% of the mice that were pre-immunized with the edible HPV16 vaccine showed positive serum IgG responses, while none of the negative controls showed any response. Vaginal IgG and IgA antibodies were also elicited in 33 and 39%, respectively, of the mice that were given with the edible HPV16 vaccine and the intranasal boost. All of the antibodies reacted more strongly to intact HPV16-VLP than to denatured HPV16-L1 protein suggesting that the edible vaccine primes for antibody responses against conformation-dependent epitopes. The inclusion of adjuvant in the vaccine formulation marginally increased the genital IgA response (P=0.06). HPV16-L1 protein in the yeast might induce tolerance in the vaccinated animals that could be recovered by intranasal boosting with a suboptimal dose of HPV-VLP. This freeze-dried yeast system may be useful as an oral delivery of HPV 16 L1 protein.
authors.affiliation: Health Science, School of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan. tsasa@med.kanazawa-u.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasagawa
authors.forename: Mayuko
authors.initials: M
authors.lastname: Tani
authors.forename: Walid
authors.initials: W
authors.lastname: Basha
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rose
authors.forename: Hideki
authors.initials: H
authors.lastname: Tohda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Giga-Hama
authors.forename: Khadijeh K
authors.initials: KK
authors.lastname: Azar
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yasuda
authors.forename: Akemi
authors.initials: A
authors.lastname: Sakai
authors.forename: Masaki
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001427:Bacterial Toxins / Q000276:immunology; D036022:Capsid Proteins / Q000008:administration & dosage / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D029968:Escherichia coli Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D022462:Vaccines, Edible / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014621:Vagina / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D036022:Capsid Proteins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D022462:Vaccines, Edible; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C063317:L1 protein, Human papillomavirus type 16; C027538:heat-labile enterotoxin, E coli