Development and immunological evaluation of an mRNA-based vaccine targeting Naegleria fowleri for the treatment of primary amoebic meningoencephalitis.
Sci Rep
; 14(1): 767, 2024 01 08.
Article
em En
| MEDLINE
| ID: mdl-38191579
ABSTRACT
More than 95% of patients fall victim to primary amoebic meningoencephalitis (PAM), a fatal disease attacking the central nervous system. Naegleria fowleri, a brain-eating microorganism, is PAM's most well-known pathogenic ameboflagellate. Despite the use of antibiotics, the fatality rate continues to rise as no clinical trials have been conducted against this disease. To address this, we mined the UniProt database for pathogenic proteins and selected assumed epitopes to create an mRNA-based vaccine. We identified thirty B-cell and T-cell epitopes for the vaccine candidate. These epitopes, secretion boosters, subcellular trafficking structures, and linkers were used to construct the vaccine candidate. Through predictive modeling and confirmation via the Ramachandran plot (with a quality factor of 92.22), we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index 0.394, instability index 38.99, antigenicity 0.8). The theoretical model of immunological simulations indicated favorable responses from both innate and adaptive immune cells, with memory cells expected to remain active for up to 350 days post-vaccination, while the antigen was eliminated from the body within 24 h. Notably, strong interactions were observed between the vaccine construct and TLR-4 (- 11.9 kcal/mol) and TLR-3 (- 18.2 kcal/mol).
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
4_TD
Base de dados:
MEDLINE
Assunto principal:
Naegleria fowleri
/
Infecções Protozoárias do Sistema Nervoso Central
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2024
Tipo de documento:
Article