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Effects of immunization with the rNfa1 protein on experimental Naegleria fowleri-PAM mice
1Department of Microbiology, and Molecular Science and Technology, Ajou University School of Medicine, Suwon, Korea.
Abstract:
Free-living Naegleria fowleri causes primary amoebic meningoencephalitis (PAM) in humans and animals. To examine the effect of immunization with Nfa1 protein on experimental murine PAM because of N. fowleri, BALB/c mice were intra-peritoneally or intra-nasally immunized with a recombinant Nfa1 protein. We analysed Nfa1-specific antibody and cytokine induction, and the mean survival time of infected mice. Mice immunized intra-peritoneally or intra-nasally with rNfa1 protein developed specific IgG, IgA and IgE antibodies; the IgG response was dominated by IgG1, followed by IgG2b, IgG2a and IgG3. High levels of the Th1 cytokine, IFN-γ, and the regulatory cytokine, IL-10, were also induced. The mean survival time of mice immunized intra-peritoneally with rNfa1 protein was prolonged compared with controls, (25.0 and 15.5 days, respectively). Similarly, the mean survival time of mice immunized intra-nasally with rNfa1 protein was 24.7 days, compared with 15.0 days for controls.
Insights
Immunizing mice with the Nfa1 protein protected against primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri. Vaccination with Nfa1 protein extended survival times in mice challenged with this deadly pathogen.
Area of Science:
- Immunology
- Infectious Diseases
- Neuroscience
Background:
- Naegleria fowleri is a free-living amoeba responsible for primary amoebic meningoencephalitis (PAM), a severe and often fatal human infection.
- Current treatment options for PAM are limited, highlighting the need for effective preventative strategies.
Purpose of the Study:
- To evaluate the efficacy of immunization with recombinant Nfa1 protein in a murine model of Naegleria fowleri infection.
- To assess the immune responses, including antibody and cytokine induction, following Nfa1 protein immunization.
Main Methods:
- BALB/c mice were immunized with recombinant Nfa1 protein via intraperitoneal or intranasal routes.
- Mice were subsequently infected with Naegleria fowleri, and their survival times were monitored.
- Nfa1-specific antibody isotypes (IgG, IgA, IgE) and Th1/regulatory cytokine levels (IFN-γ, IL-10) were analyzed.
Main Results:
- Intraperitoneal and intranasal immunization with rNfa1 protein elicited specific IgG, IgA, and IgE antibody responses.
- The IgG response was predominantly IgG1, with contributions from IgG2b, IgG2a, and IgG3.
- Significant induction of the Th1 cytokine IFN-γ and the regulatory cytokine IL-10 was observed.
- Immunization significantly prolonged the mean survival time of mice challenged with N. fowleri compared to control groups.
Conclusions:
- Immunization with Nfa1 protein can induce protective immune responses against Naegleria fowleri infection in mice.
- The Nfa1 protein holds potential as a candidate for a vaccine against primary amoebic meningoencephalitis.
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