title: The contribution of NT-gp96 as an adjuvant for increasing HPV16 E7-specific immunity in C57BL /6 mouse model.
abstract: To control cervical cancer, efficient vaccination against human papillomavirus (HPV) is highly required. Despite the advantages and safety of the protein vaccines, additional strategies to enhance their immunogenicity are needed. E7 is a transforming protein which represents a perfect target antigen for vaccines or immunotherapies. Heat shock proteins (HSPs) facilitate cellular immune responses to antigenic peptides or proteins bound to them. Regarding to previous studies, vaccination with purified HSP/antigen complexes efficiently elicit antigen-specific immune responses in mice model. The N-terminal of glycoprotein 96 (NT-gp96) has adjuvant effect and can induce effective cumulative immune response against clinical disorders, especially cancers. In this study, the recombinant HPV16 E7 and E7 linked to NT-gp96 (E7-NT-gp96) proteins were generated in prokaryotic expression system. Mice were vaccinated twice with this recombinant proteins and the immunogenicity of the fusion protein was determined. The preventive efficacy of E7-NT-gp96 fusion protein was also evaluated and compared to E7 protein after challenging with cancerous TC-1 cell line. In vitro re-stimulated splenocytes of mice vaccinated with rE7-NT-gp96 protein induced higher IFN-γ response in comparison with E7 protein immunization. Moreover, immunization with E7-NT-gp96 protein displayed low but stable humoral responses at post-challenge time. The data showed that vaccination with fused E7-NT-gp96 protein delayed the tumour occurrence and growth as compared to protein E7 alone. These results suggest that fused adjuvant-free E7-NT-gp96 protein vaccination could direct the immune responses towards Th1 immunity. Furthermore, the linkage of NT-gp96 to E7 could enhance protective anti-tumour immunity.
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: E
authors.initials: E
authors.lastname: Mohit
authors.forename: A
authors.initials: A
authors.lastname: Bolhassani
authors.forename: F
authors.initials: F
authors.lastname: Zahedifard
authors.forename: Y
authors.initials: Y
authors.lastname: Taslimi
authors.forename: S
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007114:Immunization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D018709:Statistics, Nonparametric; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D006023:Glycoproteins; D050725:Papillomavirus E7 Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16