Design of novel multi-epitope vaccines against severe acute respiratory syndrome validated through multistage molecular interaction and dynamics

Abstract

2019)Design of novel multi-epitope vaccines against severe acute respiratory syndrome validated through multistage molecular interaction and dynamics, Journal of Biomolecular Structure and Dynamics, 37:16, 4345-4360, ABSTRACT Severe acute respiratory syndrome (SARS) is endemic in South China and is continuing to spread worldwide since the 2003 outbreak, affecting human population of 37 countries till present. SARS is caused by the severe acute respiratory syndrome Coronavirus (SARS-CoV). In the present study, we have designed two multi-epitope vaccines (MEVs) composed of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B cell epitopes overlap, bearing the potential to elicit cellular as well as humoral immune response. We have used truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 as molecular adjuvants at N-terminal of both the MEVs. Selected overlapping epitopes of both the MEVs were further validated for stable molecular interactions with their respective human leukocyte antigen class I and II allele binders. Moreover, CTL epitopes were further studied for their molecular interaction with transporter associated with antigen processing. Furthermore, after tertiary structure modelling, both the MEVs were validated for their stable molecular interaction with Toll-like receptors 2 and 4. Codon-optimized cDNA of both the MEVs was analysed for their potential high level of expression in the mammalian cell line (Human) needed for their further in vivo testing. Overall, the present study proposes in silico validated design of two MEVs against SARS composed of specific epitopes with the potential to cause a high level of SARS-CoV specific cellular as well as humoral immune response.

Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: anin silicoapproach

“…The theoretical isoelectric points (PI) of the subject proteins were 6.24, 5.56 and 5.70, respectively. Protparam computed instability-index (II) of the S protein of SARS-CoV-2, SARS-CoV and MERS-CoV were 33.01, 32.42 and 36.60 indicating that these proteins are quite stable 4, 23 .…”

“…The tertiary (3D) structure of the vaccine candidate improved markedly after the refinement, and showed desirable properties based on Ramachandran plot predictions. The Ramachandran plot shows that most of the residues are found in the favoured and allowed regions (94.7%) with very few residues in the outlier region; this indicates that the quality of the overall model is satisfactory 21, 23 . The lack of allergenic properties of the CoV-RMEN further strengthens its potential as a vaccine candidate.…”

“…T-cell epitopes from RBD and NTD regions having high interaction with more HLA alleles were found to cover more than 98% of the world population with different ethnic groups 6, 37, 38 . Moreover, the molecular docking between T-cell epitopes and their respective HLA alleles revealed their highly significant binding affinity reflecting the immune activation of B- and T-cells 23 .…”

Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes

“…These epitope-based vaccines have added advantages of being safe, stable, highly specific, cost-curtailing, easy to produce in bulk, and provides option to manipulate the epitopes for designing of a better vaccine candidate [61]. This method of vaccine development has proved to be promising enough for different microbial diseases including both bacterial and viral [25,[62][63][64][65][66][67].…”

“…Here we have designed a multiepitope-based vaccine for the SARS-CoV-2 using next generation vaccinology approach where the recently available genome and proteome of the SARS-CoV-2 were maneuvered and a potential vaccine candidate was conceived. Similar strategy was employed previously for SARS-CoV and MERS-CoV [20][21][22][23][24][25] as well as certain findings are reported for the newly emerged SARS-CoV-2 [26][27][28]. While immunoinformatics techniques was utilized by groups to predict the B-cell and cytotoxic T-cell epitopes in the SARS-CoV-2 surface glycoprotein, N protein [27][28][29], others have utilized the information to design epitope-based vaccine based on the SARS-CoV-2 spike glycoprotein [26].…”