title: Enhanced humoral and CD8+ T cell immunity in mice vaccinated by DNA vaccine against human respiratory syncytial virus through targeting the encoded F protein to dendritic cells.
abstract: Human respiratory syncytial virus (RSV) is the most important cause of serious lower respiratory tract infection in infants, the elderly, and the immunocompromised population. There is no licensed vaccine against RSV until now. It has been reported that targeting antigen to DEC205, a phagocytosis receptor on dendritic cells (DCs), could induce enhanced CD4+ and CD8+ T cell responses in mice. To develop RSV DNA vaccine and target the encoded antigen protein to DCs, the ectodomain of fusion glycoprotein (sF, amino acids: 23-524) of RSV was fused with anti-DEC205 single-chain Fv fragment (scDEC) and designated scDECF. Following successful expression from the recombinant plasmid of pVAX1/scDECF, the recombinant protein of scDECF was found capable of specifically binding to DEC205 receptor on CHOmDEC205 cells, and facilitating uptake of RSV F by DC2.4 cells in vitro. Furthermore, the higher levels of RSV-specific IgG antibody responses and neutralization antibody titers, as well as RSV F-specific CD8+ T cell responses were induced in mice immunized intramuscularly by pVAX1/scDECF than by the control plasmid of pVAX1/scISOF encoding sF protein fused with isotype matched control single-chain Fv fragment (scISO). Compared with pVAX1/scISOF, both the ratio of IgG2a/IgG1, >1, and the enhanced IFN-γ cytokine were induced in mice following pVAX1/scDECF immunization, which exhibited a Th1 dominant response in pVAX1/scDECF vaccinated mice. Notably, the elevated efficiency of RSV F protein bound by DCs in vivo could also be observed in mice inoculated by pVAX1/scDECF. Collectively, these results demonstrate the enhanced IgG and CD8+T cell immune responses have been induced successfully by DNA vaccine against RSV by targeting F antigen to DCs via the DEC205 receptor, and this DC-targeting vaccine strategy merits further investigation.
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hua
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Yue-Ying
authors.initials: YY
authors.lastname: Jiao
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Xiang-Lei
authors.initials: XL
authors.lastname: Peng
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Yuan-Hui
authors.initials: YH
authors.lastname: Fu
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Yuan-Bo
authors.initials: YB
authors.lastname: Zheng
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Yan-Peng
authors.initials: YP
authors.lastname: Zheng
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hong
authors.affiliation: College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China. Electronic address: jshhe@bjtu.edu.cn.
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: He
mesh_terms: D000368:Aged; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000235:genetics; D014611:Vaccination; D019444:Vaccines, DNA; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D057127:Single-Chain Antibodies; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma
keywords: DC-targeting vaccine; DEC205; DNA vaccine; Fusion glycoprotein; Human respiratory syncytial virus