A Human Papillomavirus Type 16 Vaccine By Oral Delivery Of L1 Protein

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Journal Title, Volume, Page: 
Virus Research Volume 110, Issues 1-2, June 2005, Pages 81-90
Year of Publication: 
2005
Authors: 
Walid Basha
Health Science, School of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Current Affiliation: 
Faculty of Medicine & Health Sciences, Department of Biomedical Sciences, An-Najah National University, Nablus, Palestine
Toshiyuki Sasagawa
Health Science, School of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Mayuko Tani
Health Science, School of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Robert C. Rose
Infectious Disease Unit, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
Hideki Tohda
Central Laboratory, Asahi Glass Co, 1150 Hanezawa-cho, Kanagawa-ku, Yokohama 221-8755, Japan
Yuko Giga-Hama
Central Laboratory, Asahi Glass Co, 1150 Hanezawa-cho, Kanagawa-ku, Yokohama 221-8755, Japan
Khadijeh K. Azar
Health Science, School of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Hideyo Yasuda
Health Science, School of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Akemi Sakai
Health Science, School of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Masaki Inoue
Molecular Transplantation, Postgraduate School, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan
Preferred Abstract (Original): 

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 g 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 (1g) 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.

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