Planejamento de proteínas imunogênicas multi-epítopo visando o desenvolvimento de uma vacina de nova geração para a infecção do vírus Nipah
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2020-11-19Autor
http://lattes.cnpq.br/8367089290173036
GALÚCIO, João Marco Pereira
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Nipah (NiV) is an emerging zoonotic virus belonging to the Paramyxoviridae family, involved
with fatal respiratory and neurological diseases in humans. Recently, the World Health
Organization (WHO) declared NiV as a priority pathogen for research and development of
diagnostic, prevention, and treatment strategies. Due to the lack of effective antivirals drugs
and its potential transmissibility in humans, NiV represents a great public health challenge with
the potential risk of pandemic proliferation or application as bioterrorism agent. In the present
study, using immunoinformatics and molecular modeling approaches, we designed multiepitope proteins recognized by T and B cell lymphocytes using epitopes conserved among
known strains of NiV. The predicted epitopes were selected according to physicochemical
parameters, selectivity, and affinity binding to major histocompatibility complex (MHC)
classes I and II. Then, these polypeptide chains were bonded using residues linkers. β-defensin
adjuvants were also added to the structural models to increase immunogenicity. The
antigenicity, immunogenicity, allergenicity, as well as, the physicochemical properties of the
designed multi-epitope proteins structures were also evaluated using computational methods.
Molecular docagem and molecular dynamics simulations were performed between models
designed with four human toll-like receptors, to explore the binding mode and stability of the
TLR antigen complex. The interactions between each predicted epitope and MHC-I and MHCII structures were also analyzed, using molecular modeling. Finally, the codon adaptation of
the projected cDNA sequences and in silico expression analyzes using bacterial systems
(Escherichia coli) were performed to allow a better performance for the heterologous expression
of the immunogenic proteins. The proposed protein models were shown to be potentially
antigenic and non-allergenic; and contain immunodominant epitopes from all antigenic viral
proteins. Both molecular models have demonstrated satisfactory affinity and selectivity with
TLR3. The selected conserved and non-toxic epitopes showed a high potential to form stable
molecular interaction with various MHC molecules that cover more than 98.0% of the human
population worldwide. In addition, the analysis of the cDNA sequences of both models was
predicted with adequate expression in bacterial host lines, which could further facilitate their
heterologous expression. Together, the computer analysis provided insights into biologically
viable multiepitope proteins for candidate NiV vaccines that provide an important
understanding of the immunogenicity of viral proteins, constituting models with properties
optimized for the development of next generation vaccines.
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