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.
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.