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Vaccination with lentiviral vector expressing the nfa1 gene confers a protective immune response to mice infected with Naegleria fowleri.

Authors
Kim, JH; Sohn, HJ; Lee, J; Yang, HJ; Chwae, YJ; Kim, K; Park, S; Shin, HJ
Citation
Clinical and vaccine immunology : CVI, 20(7):1055-1060, 2013
Journal Title
Clinical and vaccine immunology : CVI
ISSN
1556-68111556-679X
Abstract
Naegleria fowleri, a pathogenic free-living amoeba, causes fatal primary amoebic meningoencephalitis (PAM) in humans and animals. The nfa1 gene (360 bp), cloned from a cDNA library of N. fowleri, produces a 13.1-kDa recombinant protein which is located on pseudopodia, particularly the food cup structure. The nfa1 gene plays an important role in the pathogenesis of N. fowleri infection. To examine the effect of nfa1 DNA vaccination against N. fowleri infection, we constructed a lentiviral vector (pCDH) expressing the nfa1 gene. For the in vivo mouse study, BALB/c mice were intranasally vaccinated with viral particles of a viral vector expressing the nfa1 gene. To evaluate the effect of vaccination and immune responses of mice, we analyzed the IgG levels (IgG, IgG1, and IgG2a), cytokine induction (interleukin-4 [IL-4] and gamma interferon [IFN-γ]), and survival rates of mice that developed PAM. The levels of both IgG and IgG subclasses (IgG1 and IgG2a) in vaccinated mice were significantly increased. The cytokine analysis showed that vaccinated mice exhibited greater IL-4 and IFN-γ production than the other control groups, suggesting a Th1/Th2 mixed-type immune response. In vaccinated mice, high levels of Nfa1-specific IgG antibodies continued until 12 weeks postvaccination. The mice vaccinated with viral vector expressing the nfa1 gene also exhibited significantly higher survival rates (90%) after challenge with N. fowleri trophozoites. Finally, the nfa1 vaccination effectively induced protective immunity by humoral and cellular immune responses in N. fowleri-infected mice. These results suggest that DNA vaccination using a viral vector may be a potential tool against N. fowleri infection.
MeSH terms
Amebiasis/immunology/*prevention & controlAnimalsAntibodies, Protozoan/bloodAntigens, Protozoan/genetics/*immunologyCentral Nervous System Protozoal Infections/immunology/*prevention & controlCytokines/secretionDisease Models, AnimalDrug Carriers/administration & dosageFemaleGenetic VectorsLentivirus/geneticsLeukocytes, Mononuclear/immunologyMiceMice, Inbred BALB CNaegleria fowleri/*immunologyProtozoan Proteins/genetics/*immunologyProtozoan Vaccines/administration & dosage/genetics/*immunologySurvival AnalysisVaccination/*methodsVaccines, DNA/administration & dosage/genetics/*immunologyVaccines, Synthetic/administration & dosage/genetics/immunology
DOI
10.1128/CVI.00210-13
PMID
23677321
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
김, 종현최, 용준김, 경민박, 선신, 호준
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