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1.
Microb Pathog ; 162: 105358, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34902539

RESUMO

Chandipura vesiculovirus (CHPV) is a fast-emerging virus that causes acute encephalitis with a high death rate. Because of its extensive prevalence in African and Asian countries, this infection has become a global hazard, and there is an urgent need to create an effective and non-allergenic vaccine or appropriate treatment to combat it. A vaccine candidate is offered utilizing a computational technique in this study. To build a potential vaccine candidate, viral protein sequences were acquired from the National Center for Biotechnology Information database and evaluated with several bioinformatics techniques to identify B-cell and T-cell epitopes. V1 was shown to be superior in terms of various physicochemical qualities, as well as highly immunogenic and non-allergic. Molecular docking revealed that the CHPV vaccine construct had a greater binding affinity with human Toll-like receptors (TLR-3 and TLR-8) and that it was stable in molecular dynamics simulations. MEC-CHPV was in silico cloned in the pET28a (+) expression vector using codon optimization. The current research identifies potential antigenic epitopes that could be used as vaccine candidates to eradicate the CHPV. This in-silico development of a CHPV vaccine with multiple epitopes could open the path for future rapid laboratory tests.


Assuntos
Epitopos de Linfócito B , Vacinas , Biologia Computacional , Epitopos de Linfócito B/genética , Epitopos de Linfócito T/genética , Humanos , Simulação de Acoplamento Molecular , Vacinas de Subunidades Antigênicas , Vesiculovirus/genética
2.
Microb Pathog ; 130: 19-37, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822457

RESUMO

H7N9, a novel strain of avian origin influenza was the first recorded incidence where a human was transited by a N9 type influenza virus. Effective vaccination against influenza A (H7N9) is a major concern, since it has emerged as a life threatening viral pathogen. Here, an in silico reverse vaccinology strategy was adopted to design a unique chimeric subunit vaccine against avian influenza A (H7N9). Induction of humoral and cell-mediated immunity is the prime concerned characteristics for a peptide vaccine candidate, hence both T cell and B cell immunity of viral proteins were screened. Antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach were adopted to generate the most antigenic epitopes of avian influenza A (H7N9) proteome. Further, a novel subunit vaccine was designed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. Physicochemical properties and secondary structure of the designed vaccine were assessed to ensure its thermostability, h ydrophilicity, theoretical PI and structural behavior. Homology modeling, refinement and validation of the designed vaccine allowed to construct a three dimensional structure of the predicted vaccine, further employed to molecular docking analysis with different MHC molecules and human immune TLR8 receptor present on lymphocyte cells. Moreover, disulfide engineering was employed to lessen the high mobility region of the designed vaccine in order to extend its stability. Furthermore, we investigated the molecular dynamic simulation of the modeled subunit vaccine and TLR8 complexed molecule to strengthen our prediction. Finally, the suggested vaccine was reverse transcribed and adapted for E. coli strain K12 prior to insertion within pET28a(+) vector for checking translational potency and microbial expression.


Assuntos
Epitopos/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/isolamento & purificação , Influenza Humana/prevenção & controle , Animais , Estabilidade de Medicamentos , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Vacinas contra Influenza/química , Vacinas contra Influenza/genética , Influenza Humana/virologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Conformação Proteica , Vacinas de Subunidades Antigênicas/química , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/isolamento & purificação , Vacinas Sintéticas/química , Vacinas Sintéticas/genética , Vacinas Sintéticas/isolamento & purificação , Vacinologia/métodos
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