Protective immunity against Naegleria fowleri infection on mice immunized with the rNfa1 protein using mucosal
Jinyoung Lee1, Jong-Kyun Yoo, Hae-Jin Sohn
1Department of Microbiology, Ajou University School of Medicine, Suwon, 443-721, Republic of Korea.
Abstract:
The free-living amoeba, Naegleria fowleri, causes a fatal disease called primary amoebic meningoencephalitis (PAM) in humans and experimental animals. Of the pathogenic mechanism of N. fowleri concerning host tissue invasion, the adherence of amoeba to hose cells is the most important. We previously cloned the nfa1 gene from N. fowleri. The protein displayed immunolocalization in the pseudopodia, especially the food-cups structure, and was related to the contact-dependent mechanism of the amoebic pathogenicity in N. fowleri infection. The cholera toxin B subunit (CTB) and Escherichia coli heat-labile enterotoxin B subunit (LTB) have been used as potent mucosal adjuvants via the parenteral route of immunization in most cases. In this study, to examine the effect of protective immunity of the Nfa1 protein for N. fowleri infection with enhancement by CTB or LTB adjuvants, intranasally immunized BALB/c mice were infected with N. fowleri trophozoites for the development of PAM. The mean time to death of mice immunized with the Nfa1 protein using LTB or CTB adjuvant was prolonged by 5 or 8 days in comparison with that of the control mice. In particular, the survival rate of mice immunized with Nfa1 plus CTB was 100% during the experimental period. The serum IgG levels were significantly increased in mice immunized with Nfa1 protein plus CTB or LTB adjuvants. These results suggest that the Nfa1 protein, with CTB or LTB adjuvants, induces strong protective immunity in mice with PAM due to N. fowleri infection.
Insights
Naegleria fowleri infection causes fatal primary amoebic meningoencephalitis (PAM). Immunizing mice with the Nfa1 protein, enhanced by CTB or LTB adjuvants, significantly improved survival rates and induced protective immunity against PAM.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Naegleria fowleri is a free-living amoeba causing fatal primary amoebic meningoencephalitis (PAM).
- Amoebic adherence to host cells is critical for N. fowleri pathogenicity.
- The Nfa1 protein, previously identified, is implicated in N. fowleri's contact-dependent pathogenicity.
Purpose of the Study:
- To evaluate the protective immunity induced by the Nfa1 protein against N. fowleri infection.
- To assess the adjuvant effects of cholera toxin B subunit (CTB) and E. coli heat-labile enterotoxin B subunit (LTB) on Nfa1-induced immunity.
Main Methods:
- BALB/c mice were intranasally immunized with Nfa1 protein combined with CTB or LTB adjuvants.
- Immunized mice were subsequently infected with N. fowleri trophozoites to induce PAM.
- Survival rates, mean time to death, and serum IgG levels were analyzed.
Main Results:
- Immunization with Nfa1 plus CTB or LTB significantly prolonged the mean time to death in mice infected with N. fowleri.
- Mice immunized with Nfa1 plus CTB exhibited a 100% survival rate during the experimental period.
- Serum IgG levels were significantly elevated in mice receiving Nfa1 with either CTB or LTB adjuvant.
Conclusions:
- The Nfa1 protein, when administered with CTB or LTB adjuvants, effectively induces protective immunity against Naegleria fowleri infection.
- CTB and LTB act as potent mucosal adjuvants, enhancing the immunogenicity of the Nfa1 protein for PAM prevention.
