title: Construction and immunological characterization of CD40L or GM-CSF incorporated Hantaan virus like particle.
abstract: Infection of Hantaan virus (HTNV) usually causes hemorrhagic fever with renal syndrome (HFRS). China has the worst epidemic incidence of HFRS as well as high fatality. Inactivated whole virus has been used for HFRS vaccination, however there are still problems such as safety concerns. CD40 ligand (CD40L) and granulocyte macrophage colony-stimulating factor (GM-CSF) are well-known immune stimulating molecules that can enhance antigen presenting, lymphocytes activation and maturation, incorporation of CD40L and GM-CSF to the surface of virus like particles (VLPs) can greatly improve the vaccination effect. We constructed eukaryotic vectors expressing HTNV M segment and S segment, as well as vectors expressing HTNV M segment with CD40L or GM-CSF, our results showed successful production of CD40L or GM-CSF incorporated HTNV VLPs. In vitro stimulation with CD40L or GM-CSF anchored HTNV VLP showed enhanced activation of macrophages and DCs. CD40L/GM-CSF incorporated VLP can induce higher level of HTNV specific antibody and neutralizing antibody in mice. Immunized mice splenocytes showed higher ability of secreting IFN-γ and IL-2, as well as enhancing CTL activity. These results suggest CD40L/GM-CSF incorporated VLP can serve as prospective vaccine candidate.
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Qikang
authors.initials: Q
authors.lastname: Ying
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
authors.forename: Agnieszka D
authors.initials: AD
authors.lastname: Truax
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Statistics, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xingan
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000378:metabolism; D000914:Antibodies, Viral / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000008:administration & dosage*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D018063:Hantaan virus / Q000276:immunology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007376:Interleukin-2; D058425:Vaccines, Virus-Like Particle; D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: CD40 ligand; granulocyte macrophage colony-stimulating factor; virus like particle; virus vaccine; Hantaan virus