title: Characterization and evaluation of the immune responses elicited by a novel human papillomavirus (HPV) therapeutic vaccine: HPV 16E7-HBcAg-Hsp65 fusion protein.
abstract: Human papillomaviruses (HPV), particularly HPV16, are associated with most cervical cancers. Currently, although prophylactic vaccines have been developed, there is still an urgent need to develop therapeutic HPV vaccines. In this study, a novel fusion protein, HPV 16 E7-HBcAg-Hsp65 (VR111), with the goal of increasing anti-HPV16 cellular immunity was developed. VR111 was analyzed using SDS-PAGE, western-blotting, capillary isoelectric focusing (cIEF), analytical ultracentrifugation (AUC) and dynamic light scattering (DLS). Gamma interferon (IFN-γ) secretion assay was performed by enzyme-linked immunospot (ELISPOT) and ELISA to test their ability to induce cellular immune response. Significant correlation between ELISPOT and ELISA was observed (r=0.8680, p<0.0001). It was shown that VR111 could induce a significant increase in E7-specific CD8(+) T cell responses. Humoral immune response was also observed. The antibody titer levels were measured by ELISA. These results indicated that VR111 was a promising therapeutic vaccine for treatment of cervical cancer with possible therapeutic potential in clinical settings.
authors.affiliation: Department of Quality Research, Shanghai Zerun Biotechnology Co., Ltd. , No. 1399, Zhangheng Road, Shanghai 201203, China. Electronic address: zhoucmzsp@126.com.
authors.forename: Chao-Ming
authors.initials: CM
authors.lastname: Zhou
authors.affiliation: Department of Quality Research, Shanghai Zerun Biotechnology Co., Ltd. , No. 1399, Zhangheng Road, Shanghai 201203, China.
authors.forename: Gao-Xia
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Department of Quality Research, Shanghai Zerun Biotechnology Co., Ltd. , No. 1399, Zhangheng Road, Shanghai 201203, China.
authors.forename: Xin-Xing
authors.initials: XX
authors.lastname: Ma
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics; D006512:Hepatitis B Core Antigens / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology; D030361:Papillomavirus Infections / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D018834:Chaperonin 60; D024101:Mitochondrial Proteins
chemical_list: D000914:Antibodies, Viral; D006360:Heat-Shock Proteins; D006512:Hepatitis B Core Antigens; D007371:Interferon-gamma; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16; C060293:HSPD1 protein, human; D018834:Chaperonin 60; D024101:Mitochondrial Proteins
keywords: Cellular immune response; Human papillomaviruses; Humoral immune response; Immunogenicity; Therapeutic vaccine