Top Down Computational Approach: A Vaccine Development Step to Find Novel Superantigenic HLA Binding Epitopes from Dengue Virus Proteome

Abstract

Dengue virus (DENV) is a major mosquito vector based human pathogenic flavivirus which is causing major threat worldwide, yet the availability of therapeutic treatment and several vaccines, still called for advance treatment and vaccine development. The present top down computational approach is a vaccine development step to find novel super antigenic HLA binding epitopes from DENV proteome. The approach used sequence based screening to find complete conserve and high population coverage, common epitopes among all DENV serotype. Propred and Immune Epitope Data Base were used for sequence based screening with recommended parameters. Among top 29 identified epitopes, five structural protein epitopes viz. 33 LQGRGPLKL 41 , 249 VVVLGSQEG 257 , 172 LVGIVTLYL 180 , 146 MKILIGVVI 154 , 72 YIIVGVEPG 80 and one nonstructural protein epitope 18 LKNDIPMTG 26 were showed high conserve nature and high population coverage from complete DENV proteome. Further structure based study involving docking and molecular dynamic simulation to confirm stable behavior of HLA allele–peptide complex to give potent cell mediated immune response. Docking of epitope 72 YIIVGVEPG 80 –DRB1 0401 allele and epitope 33 LQGRGPLKL 41 –B*5101 allele complexes showed the best binding energy of − 7.71 and − 7.20 kcal/mol, respectively and stable binding pattern over the time window during molecular dynamic simulation. This computational approach resulted novel epitopes which can be used in the design and development of short epitope based vaccines as well as diagnosis tools for dengue infection.

Chikungunya Virus Vaccine Development: Through Computational Proteome Exploration for Finding of HLA and cTAP Binding Novel Epitopes as Vaccine Candidates

“…The extracted promising conserve epitopes will studied for binding analysis to all HLA alleles supertype groups in comparison with already known superantigen positive controls to validate epitopes super-antigenicity. The known + ve controls which have been taken in the study are 141 STLPETTVV 149 peptide of Hepatitis core protein (Accession No.CAA59535) and 265 ILRGSVAHK 273 peptide of H1N1 Nucleoprotein (P03466) (Sharma et al 2021 ; Ansari et al 2009 ). This study was done by using IEDB platform.…”

“…During development of epitope based vaccine, screening of highly conserved epitopes along with different supertypes alleles binding analysis strengthened the finding of best superantigen as vaccine reagents which were already shown in several other viruses vaccine development such as H1N1, JEV, DENGUE and WNV etc. ( Kumar et al 2013 ; Sharma et al 2014 , 2021 ). Recently, other than these human pathogens zika virus, fungal pathogen as well as veterinary pathogens also showed potential results in development of epitope vaccine (Sharma et al 2019 ; Jain et al 2021 ).…”

Design of multi-epitope vaccine candidate against Brucella type IV secretion system (T4SS)

“…As there is currently no Brucella vaccine for humans. Therefore, it is vital to develop a more effective and safer vaccine for humans [ 50 ]. We have constructed a new specific multi-epitope vaccine based on the structural basis of the Brucella type IV secretion system.…”

Design of multi-epitope vaccine candidate against Brucella type IV secretion system (T4SS)

“…Brucellosis is a debilitating zoonotic disease that can cause significant economic losses in livestock populations worldwide [38,39] .As there is currently no brucella vaccine for humans, it is vital to develop a more effective and safer vaccine for humans [40] .The type IV secretion system (T4SS), encoded by the virB manipulator, is an important virulence factor for Brucella abortus, while its core component consists of VirB6-VirB1016.VirB8 is a two-site endosomal protein that plays a critical role in the nucleation of T4SS channels [41,42]. VirB10 is a bilayer protein inserted into the bacterial endosome, and the proline-rich region plays a key role in core complex assembly and substrate secretion [43,44] .…”