Vaccination with Lentiviral Vector Expressing the<i>nfa1</i>Gene Confers a Protective Immune Response to Mice Infected with Naegleria fowleri

Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Jin Young; Yang, Hee-Jong; Chwae, Yong‐Joon; Kim, Kyongmin; Park, Sun; Shin, Ho‐Joon

doi:10.1128/cvi.00210-13

Cited by 15 publications

(7 citation statements)

References 34 publications

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“…The results showed that cytokine production, production of specific IgG and IgG subclasses (IgG1 and IgG2a) are strongly enhanced by nfa1 vaccination, and the increase in survival rate (90%) of mice infected with N. fowleri trophozoites has also been observed. Furthermore, this study suggested that for the treatment of N. fowleri infection, nfa1 vaccination could be a new potential tool . Another study revealed that protective immune responses can be obtained by immunization of mice with rNfa1 protein.…”

Section: Managementmentioning

confidence: 86%

“…Furthermore, this study suggested that for the treatment of N. fowleri infection, nfa1 vaccination could be a new potential tool. 97 Another study revealed that protective immune responses can be obtained by immunization of mice with rNfa1 protein. The results obtained from this study indicated that for the treatment as well as vaccination against N. fowleri infection, Nfa1 protein is a candidate antigen.…”

Section: Molecular Based Targets and Vaccination Strategies To Manamentioning

confidence: 99%

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Naegleria fowleri: Sources of infection, pathophysiology, diagnosis, and management; a review

Jahangeer

Mahmood

Munir

et al. 2019

Clin Exp Pharma Physio

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Naegleria fowleri, a thermophilic flagellate amoeba known as a “brain‐eating” amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as primary amoebic meningoencephalitis (PAM), both in humans as well as in animals. PAM is a rare but fatal disease affecting young adults all around the world, particularly in the developed world but recently reported from developing countries, with 95%–99% mortality rate. Swimmers and divers are at high risk of PAM as the warm water is the most propitious environment adapted by N. fowleri to cause this infection. Infective amoeba in the trophozoite phase enter the victim's body through the nose, crossing the cribriform plate to reach the human brain and cause severe destruction of the central nervous system (CNS). The brain damage leads to brain haemorrhage and death occurs within 3–7 days in undiagnosed cases and maltreated cases. Though the exact pathogenesis of N. fowleri is still not known, it has exhibited two primary mechanisms, contact‐independent (brain damage through different proteins) and contact‐dependent (brain damage through surface structures food cups), that predominantly contribute to the pathogen invading the host CNS. For the management of this life‐threatening infection different treatment regimens have been applied but still the survival rate is only 5% which is ascribed to its misdiagnosis, as the PAM symptoms closely resembled bacterial meningitis. The main objectives of this review article are to compile data to explore the sources and routes of N. fowleri infection, its association in causing PAM along with its pathophysiology; latest techniques used for accurate diagnosis, management options along with challenges for Pakistan to control this drastic disorder.

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Section: Managementmentioning

confidence: 86%

Section: Molecular Based Targets and Vaccination Strategies To Manamentioning

confidence: 99%

Naegleria fowleri: Sources of infection, pathophysiology, diagnosis, and management; a review

Jahangeer

Mahmood

Munir

et al. 2019

Clin Exp Pharma Physio

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“…Because actin is localized around food cups and has been shown to have the capacity to modulate in vitro cytotoxicity in different target cells, it is frequently discussed as a potential pathogenicity factor in N. fowleri [ 11 – 16 , 18 ]. Furthermore, the effects of immunization with either a DNA vaccine or a lentiviral vector expressing the nfa1 gene ( N. fowleri actin 1) were investigated in mice infected with PAM [ 42 , 43 ]. In the present study, actin 1 and actin 2 were found to be up-regulated in highly pathogenic trophozoites in 2D gels (Figure 3 , Table 3 ), confirming the potential role of actin in the pathogenic mechanisms of N. fowleri.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri

et al. 2014

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BackgroundThe free-living amoeba Naegleria fowleri is the causative agent of the rapidly progressing and typically fatal primary amoebic meningoencephalitis (PAM) in humans. Despite the devastating nature of this disease, which results in > 97% mortality, knowledge of the pathogenic mechanisms of the amoeba is incomplete. This work presents a comparative proteomic approach based on an experimental model in which the pathogenic potential of N. fowleri trophozoites is influenced by the compositions of different media.ResultsAs a scaffold for proteomic analysis, we sequenced the genome and transcriptome of N. fowleri. Since the sequence similarity of the recently published genome of Naegleria gruberi was far lower than the close taxonomic relationship of these species would suggest, a de novo sequencing approach was chosen. After excluding cell regulatory mechanisms originating from different media compositions, we identified 22 proteins with a potential role in the pathogenesis of PAM. Functional annotation of these proteins revealed, that the membrane is the major location where the amoeba exerts its pathogenic potential, possibly involving actin-dependent processes such as intracellular trafficking via vesicles.ConclusionThis study describes for the first time the 30 Mb-genome and the transcriptome sequence of N. fowleri and provides the basis for the further definition of effective intervention strategies against the rare but highly fatal form of amoebic meningoencephalitis.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-496) contains supplementary material, which is available to authorized users.

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“…Naegleria fowleri is a free‐living ameboflagellate found throughout the world in diverse habitats such as soil, temperate waters, lakes and ponds 1,2 . This species is the aetiological agent of primary amoebic meningoencephalitis (PAM), an acute fatal infection in humans and animals initiated in the nasal mucosa that causes a rapid progression of the disease that usually results in the death of infected people in a period of 1‐2 weeks 3 . Most infections caused by N fowleri have been reported in children and young adults with a recent history of swimming principally during the summer months 4 .…”

Section: Introductionmentioning

confidence: 99%

Identification of differential protein recognition pattern between Naegleria fowleri and Naegleria lovaniensis

Gutiérrez‐Sánchez

Carrasco-Yépez

Herrera‐Díaz

et al. 2020

Parasite Immunology

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Many pathogenicity factors are involved in the development of primary amoebic meningoencephalitis (PAM) caused by N fowleri. However, most of them are not exclusive for N fowleri and they have not even been described in other nonpathogenic Naegleria species. Therefore, the objective of this work was to identify differential proteins and protein pattern recognition between Naegleria fowleri and Naegleria lovaniensis using antibodies anti‐N fowleri as strategy to find vaccine candidates against meningoencephalitis. Electrophoresis and Western blots conventional and 2‐DE were performed for the identification of antigenic proteins, and these were analysed by the mass spectrometry technique. The results obtained in 2‐DE gels and Western blot showed very notable differences in spot intensity between these two species, specifically those with relative molecular weight of 100, 75, 50 and 19 kDa. Some spots corresponding to these molecular weights were identified as actin fragment, myosin II, heat shock protein, membrane protein Mp2CL5 among others, with differences in theoretical post‐translational modifications. In this work, we found differences in antigenic proteins between both species, proteins that could be used for a further development of vaccines against N fowleri infection.

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Vaccination with Lentiviral Vector Expressing thenfa1Gene Confers a Protective Immune Response to Mice Infected with Naegleria fowleri

Cited by 15 publications

References 34 publications

Naegleria fowleri: Sources of infection, pathophysiology, diagnosis, and management; a review

Naegleria fowleri: Sources of infection, pathophysiology, diagnosis, and management; a review

Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri

Identification of differential protein recognition pattern between Naegleria fowleri and Naegleria lovaniensis

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