title: Whole recombinant Pichia pastoris expressing HPV16 L1 antigen is superior in inducing protection against tumor growth as compared to killed transgenic Leishmania.
abstract: The development of an efficient vaccine against high-risk HPV types can reduce the incidence rates of cervical cancer by generating anti-tumor protective responses. Traditionally, the majority of prophylactic viral vaccines are composed of live, attenuated or inactivated viruses. Among them, the design of an effective and low-cost vaccine is critical. Inactivated vaccines especially heat-killed yeast cells have emerged as a promising approach for generating antigen-specific immunotherapy. Recent studies have indicated that yeast cell wall components possess adjuvant activities. Moreover, a non-pathogenic protozoan, Leishmania tarentolae (L.tar) has attracted a great attention as a live candidate vaccine. In current study, immunological and protective efficacy of whole recombinant killed Pichia pastoris and Leishmania tarentolae expressing HPV16 L1 capsid protein was evaluated in tumor mice model. We found that Pichia-L1, L.tar-L1 and Gardasil groups increase the IgG2a/IgG1 ratio, indicating a relative preference for the induction of Th1 immune responses. Furthermore, subcutaneous injection of killed Pichia-L1 generated the significant L1-specific IFN-γ immune response as well as the best protective effects in vaccinated mice as compared to killed L.tar-L1, killed Pichia pastoris, killed L.tar and PBS groups. Indeed, whole recombinant Leishmania tarentolae could not protect mice against C3 tumor mice model. These data suggest that Pichia-L1 may be a candidate for the control of HPV infections.
authors: a Department of Hepatitis and AIDs; Pasteur Institute of Iran ; Tehran , Iran. azam.bolhassani@yahoo.com
authors: Azam
authors: A
authors: Bolhassani
authors: Martin
authors: M
authors: Muller
authors: Farzin
authors: F
authors: Roohvand
authors: Fatemeh
authors: F
authors: Motevalli
authors: Elnaz
authors: E
authors: Agi
authors: Mehdi
authors: M
authors: Shokri
authors: Mahdieh Motamedi
authors: MM
authors: Rad
authors: Sahar
authors: S
authors: Hosseinzadeh
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007891:Leishmania / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D010843:Pichia / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014771:Virion / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C063317:L1 protein, Human papillomavirus type 16; D007371:Interferon-gamma
keywords: 2-ME, mercaptoethanol; AOX1, alcohol oxidase I gene; ConA, concanavalin A; DAB, 3,3′-diaminobenzidine; FACS, fluorescence-activated cell sorting; GFP, green fluorescent protein; HPV, human papillomaviruses; KBMA, killed but metabolicallyactive; L.tar, Leishmania tarentolae; L1 capsid protein; Leishmania tarentolae expression system; Pichia pastoris expression system; SD, standard deviation; Yeast-HBsAg, yeast expressing hepatitis B surface antigen; cervical cancer; human papillomavirus; killed vaccine; rL1, recombinant L1