Banca de DEFESA: JOÃO MARCOS PEREIRA GALÚCIO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : JOÃO MARCOS PEREIRA GALÚCIO
DATA : 19/11/2020
HORA: 14:00
LOCAL: sala virtual
TÍTULO:

MULTI-EPITOPO IMMUNOGENIC PROTEIN PLANNING AIMING AT THE DEVELOPMENT OF A NEW GENERATION VACCINE FOR NIPAH VIRUS INFECTION

PALAVRAS-CHAVES:

Henipavirus. Immunoinformatics. Multi-epitope vaccines. Molecular modelling.

PÁGINAS: 50
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biotecnologia
RESUMO:

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 multi-epitope 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 fused 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 MHC-II 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.

MEMBROS DA BANCA:
Presidente - 1770373 - PAULO SERGIO TAUBE JUNIOR
Externo à Instituição - RODOLPHO DE CAMPOS BRAGA - UFG
Externo à Instituição - ÉLCIO DE SOUZA LEAL