Effect of DNA Vaccination with Retroviral Vector Expressing nfa1 Gene in Naegleria fowleri Infection
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초록
Naegleria fowleri is pathogenic free-living amoeba leading to primary amoebicmeningoencephalitis(PAM) in human and animals. The nfa1 gene cloned from N. fowleri islocated on food-cup structure called pseudopodia and function an adherence of host targetcells. To evaluate the effect of nfa1 vaccination against N. fowleri infection, we constructedretroviral vector(pQCXIN) expressing nfa1 gene. To determine the effect of vaccination andprotective immunity in in vivo models, we measured the immunoglobulin levels, cytokineinduction, and survival rate in mice infected with N. fowleri. Both levels of IgG and IgGsubclass in DNA vaccinated mice were significantly elevated. The cytokine analysis showthat DNA vaccinated mice induces production of IL-4 and IFN-γcytokines suggesting aTh1/Th2 mixed type immune response. The levels of nfa1 specific IgG antibody weremaintained highly until 12 weeks post-vaccination in vaccinted mice. The nfa1 vaccinatedmice using retroviral vector increased significantly survival rate(60%) after N. fowleri infection. Consequently, the nfa1 vaccination effectively induces protective immunity by upregulation ofimmune response in mice infected with N. fowleri. These results suggest that DNAvaccination using retroviral vector may be proper trial for treatment and prevention of PAM.
Abstract
Naegleria fowleri is pathogenic free-living amoeba leading to primary amoebicmeningoencephalitis(PAM) in human and animals. The nfa1 gene cloned from N. fowleri islocated on food-cup structure called pseudopodia and function an adherence of host targetcells. To evaluate the effect of nfa1 vaccination against N. fowleri infection, we constructedretroviral vector(pQCXIN) expressing nfa1 gene. To determine the effect of vaccination andprotective immunity in in vivo models, we measured the immunoglobulin levels, cytokineinduction, and survival rate in mice infected with N. fowleri. Both levels of IgG and IgGsubclass in DNA vaccinated mice were significantly elevated. The cytokine analysis showthat DNA vaccinated mice induces production of IL-4 and IFN-γcytokines suggesting aTh1/Th2 mixed type immune response. The levels of nfa1 specific IgG antibody weremaintained highly until 12 weeks post-vaccination in vaccinted mice. The nfa1 vaccinatedmice using retroviral vector increased significantly survival rate(60%) after N. fowleri infection. Consequently, the nfa1 vaccination effectively induces protective immunity by upregulation ofimmune response in mice infected with N. fowleri. These results suggest that DNAvaccination using retroviral vector may be proper trial for treatment and prevention of PAM.
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