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1.
BMC Genomics ; 25(1): 791, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160492

RESUMO

Acinetobacter baumannii is a gram-negative bacillus prevalent in nature, capable of thriving under various environmental conditions. As an opportunistic pathogen, it frequently causes nosocomial infections such as urinary tract infections, bacteremia, and pneumonia, contributing to increased morbidity and mortality in clinical settings. Consequently, developing novel vaccines against Acinetobacter baumannii is of utmost importance. In our study, we identified 10 highly conserved antigenic proteins from the NCBI and UniProt databases for epitope mapping. We subsequently screened and selected 8 CTL, HTL, and LBL epitopes, integrating them into three distinct vaccines constructed with adjuvants. Following comprehensive evaluations of immunological and physicochemical parameters, we conducted molecular docking and molecular dynamics simulations to assess the efficacy and stability of these vaccines. Our findings indicate that all three multi-epitope mRNA vaccines designed against Acinetobacter baumannii are promising; however, further animal studies are required to confirm their reliability and effectiveness.


Assuntos
Acinetobacter baumannii , Vacinas Bacterianas , Biologia Computacional , Acinetobacter baumannii/imunologia , Acinetobacter baumannii/genética , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/genética , Biologia Computacional/métodos , Epitopos/imunologia , Epitopos/química , Simulação de Acoplamento Molecular , Infecções por Acinetobacter/prevenção & controle , Infecções por Acinetobacter/imunologia , Mapeamento de Epitopos , Vacinas de mRNA , Simulação de Dinâmica Molecular , Humanos , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/química
2.
Med Mycol ; 62(8)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39122658

RESUMO

Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While C. neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of C. neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte (cytotoxic T lymphocyte and helper T lymphocyte) and B lymphocyte epitopes derived from four C. neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to Toll-like receptor 4 ( and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine's capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against C. neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.


A multi-epitope Cryptococcus neoformans vaccine covering the most common A and D phenotypes was designed using bioinformatics methods.


Assuntos
Biologia Computacional , Cryptococcus neoformans , Epitopos de Linfócito B , Epitopos de Linfócito T , Vacinas Fúngicas , Simulação de Acoplamento Molecular , Cryptococcus neoformans/imunologia , Cryptococcus neoformans/química , Vacinas Fúngicas/imunologia , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito B/imunologia , Humanos , Criptococose/imunologia , Criptococose/prevenção & controle , Receptor 4 Toll-Like/imunologia , Antígenos de Fungos/imunologia , Simulação de Dinâmica Molecular , Adjuvantes Imunológicos , Imunoinformática
3.
Int Immunopharmacol ; 135: 112242, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38772296

RESUMO

The emergence of Cryptococcus neoformans has posed an undeniable burden to many regions worldwide, with its strains mainly entering the lungs through the respiratory tract and spreading throughout the body. Limitations of drug regimens, such as high costs and limited options, have directed our attention toward the promising field of vaccine development. In this study, the subtractive proteomics approach was employed to select target proteins from databases that can accurately cover serotypes A and D of the Cryptococcus neoformans. Further, two multi-epitope vaccines consisting of T and B cell epitopes were demonstrated that they have good structural stability and could bind with immune receptor to induce desired immune responses in silico. After further evaluation, these vaccines show the potential for large-scale production and applicability to the majority of the population of the world. In summary, these two vaccines have been theoretically proven to combat Cryptococcus neoformans infections, awaiting further experimental validation of their actual protective effects.


Assuntos
Biologia Computacional , Criptococose , Cryptococcus neoformans , Epitopos de Linfócito B , Vacinas Fúngicas , Proteômica , Cryptococcus neoformans/imunologia , Vacinas Fúngicas/imunologia , Proteômica/métodos , Criptococose/imunologia , Criptococose/prevenção & controle , Humanos , Biologia Computacional/métodos , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Animais , Antígenos de Fungos/imunologia , Proteínas Fúngicas/imunologia , Proteínas Fúngicas/química , Desenvolvimento de Vacinas , Imunoinformática
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