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Two MP2CL5 Antigen Vaccines from Naegleria fowleri Stimulate the Immune Response against Meningitis in the BALB/c
Mara Gutiérrez-Sánchez1, María Maricela Carrasco-Yépez2, José Correa-Basurto3
1Laboratorio de Inmunobiología Molecular y Celular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico.
Abstract:
Naegleria fowleri is an etiological agent that generates primary amoebic meningoencephalitis; unfortunately, no effective treatment or vaccine is available. The objective of this work was to determine the immunoprotective response of two vaccine antigens, as follows: (i) the polypeptide band of 19 kDa or (ii) a predicted immunogenic peptide from the membrane protein MP2CL5 (Smp145). Both antigens were administered intranasally in mice using cholera toxin (CT) as an adjuvant. The survival rate and immune response of immunized mice with both antigens and challenged with N. fowleri trophozoites were measured in the nose-associated lymphoid tissue (NALT) and nasal passages (NPs) by flow cytometry and enzyme-linked immunosorbent assay (ELISA). We also determined the immunolocalization of both antigens in N. fowleri trophozoites by confocal microscopy. Immunization with the polypeptide band of 19 kDa alone or coadministered with CT was able to confer 80% and 100% of protection, respectively. The immunization with both antigens (alone or coadministered with CT) showed an increase in T and B lymphocytes. In addition, there was an increase in the expression of integrin α4β1 and IgA in the nasal cavity of protected mice, and the IgA, IgG, and IgM levels were increased in serum and nasal washes. The immunolocalization of both antigens in N. fowleri trophozoites was observed in the plasma membrane, specifically in pseudopod-like structures. The MP2CL5 antigens evaluated in this work were capable of conferring protection which would lead us to consider them as potential candidates for vaccines against meningitis caused by N. fowleri.
Insights
Naegleria fowleri causes primary amoebic meningoencephalitis. Immunizing mice with a 19 kDa polypeptide or MP2CL5 peptide antigen conferred significant protection against N. fowleri infection.
Area of Science:
- Immunology
- Infectious Diseases
- Vaccine Development
Background:
- Naegleria fowleri is a pathogen causing primary amoebic meningoencephalitis (PAM).
- No effective treatments or vaccines currently exist for PAM.
- Developing a vaccine against N. fowleri is a critical unmet medical need.
Purpose of the Study:
- To evaluate the immunoprotective potential of two vaccine antigens derived from N. fowleri.
- To assess the immune response in mice immunized with these antigens and challenged with N. fowleri.
- To determine the localization of these antigens within N. fowleri trophozoites.
Main Methods:
- Mice were intranasally immunized with a 19 kDa polypeptide or an MP2CL5 peptide antigen, with or without cholera toxin (CT) adjuvant.
- Immune responses were analyzed in nasal-associated lymphoid tissue (NALT) and nasal passages (NPs) using flow cytometry and ELISA.
- Antigen localization in N. fowleri trophozoites was determined by confocal microscopy.
Main Results:
- Intranasal immunization with the 19 kDa polypeptide conferred 80% protection alone and 100% protection with CT.
- Both antigens increased T and B lymphocyte populations and elevated IgA, IgG, and IgM levels in serum and nasal washes.
- Antigens were localized to the plasma membrane and pseudopod-like structures of N. fowleri trophozoites.
Conclusions:
- The evaluated MP2CL5 antigens demonstrate significant immunoprotective capabilities.
- These antigens are promising candidates for developing a vaccine against Naegleria fowleri meningitis.
- Further research into these antigens could lead to effective PAM prevention strategies.
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