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.
Highlights
Infectious Hantaan virus (HTNV) is a major cause of hemorrhagic fever with renal syndrome (HFRS)
In order to express CD40 ligand (CD40L)/granulocyte macrophage colony-stimulating factor (GM-CSF) in cis along with HTNV antigens, we developed the virus like particles (VLPs) by inserting the membrane bound form of a murine CD40L/GM-CSF gene downstream of the HTNV M gene of our plasmid that expresses HTNV GP
Indirect immune fluorescence analyses showed that the HTNV GP and CD40L/GM-CSF were expressed on the cell membrane after transfection (Figure 1)
Summary
Infectious Hantaan virus (HTNV) is a major cause of hemorrhagic fever with renal syndrome (HFRS). In China, it refers to about 100,000 of patients every year [1]. Inactivated whole HTNV viron has been used for HFRS vaccination, and the outcome is encouraging [2]. The inactivated vaccine still has problems with less than satisfactory levels of neutralizing antibody titer and activation of cellular immunity. In addition there are safety concerns with bringing in animal-derived virus or virulence restoration [3]. Development of new type of HFRS virus vaccine is imminent for the control of HFRS
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