title: HSP70 gene fused with Hantavirus S segment DNA significantly enhances the DNA vaccine potency against hantaviral nucleocapsid protein in vivo.
abstract: Heat shock proteins (HSPs) have been shown to act as adjuvants when coadministered with peptide antigens or given as fusion proteins and enhance the vaccination efficiency. To evaluate the enhancement of the potency of Hantaan virus (HTNV) nucleocapsid protein (NP) immunogenicity by heat shock protein 70 (HSP70), we developed a novel chimeric HTNV S-HSP70 DNA vaccine plasmid by genetically linking HSP70 gene to the full-length HTNV S segment DNA (HTNV S DNA). C57BL/6 mice were immunized with this plasmid followed by a subsequent boost with homologous recombinant protein. The levels of HTNV NP-specific antibody and cellular immune response were measured by use of ELISA, fluorescence activated cell sorter (FACS) analysis, cytotoxicity assay, and IFN-gamma ELISPOT assay. We found that HTNV S-HSP70 DNA vaccination significantly increased the levels of HTNV NP-specific antibody, IgG2a/IgG1 ratio, IFN-gamma producing CD8+ T-cell precursor frequencies, and cytotoxic T lymphocyte (CTL) response when compared with immunization with HTNV S DNA alone or HTNV S DNA physically mixed with HSP70 DNA. By contrast, HSP70 DNA or vector DNA immunization could not induce appreciable levels of specific antibodies and CTL response. Thus, we demonstrate for the first time that HSP70-based HTNV S DNA can induce both humoral and cellular immune response specific for HTNV NP and is a promising candidate DNA vaccine for HTNV infection.
authors.affiliation: Department of Pathology, Xijing Hospital, 4th Military Medical University, No. 17 Changle Xi Road, Xi'an, Shaanxi 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Zheng Xu
authors.initials: ZX
authors.lastname: Ye
authors.forename: Kai Nan
authors.initials: KN
authors.lastname: Li
authors.forename: Ji Hong
authors.initials: JH
authors.lastname: Cui
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Yun Xin
authors.initials: YX
authors.lastname: Cao
authors.forename: Yan Fang
authors.initials: YF
authors.lastname: Liu
authors.forename: Shou Jing
authors.initials: SJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019556:COS Cells; D002522:Chlorocebus aethiops; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006476:Orthohantavirus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins / Q000276:immunology*; D010957:Plasmids; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D018840:HSP70 Heat-Shock Proteins; D019590:Nucleocapsid Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma