Dataset Information

An immunoinformatics study on the spike protein of SARS-CoV-2 revealing potential epitopes as vaccine candidates.

ABSTRACT:

Background

The pandemic situation of SARS-CoV-2 infection has sparked global concern due to the disease COVID-19 caused by it. Since the first cluster of confirmed cases in China in December 2019, the infection has been reported across the continents and inflicted upon a substantial number of populations.

Method

This study is focused on immunoinformatics analyses of the SARS-CoV-2 spike glycoprotein (S protein) which is key for the viral attachment to human host cells. Computational analyses were carried out for the prediction of B-cell and T-cell (MHC class I and II) epitopes of S protein and the analyses were extended further for the prediction of their immunogenic properties. The interaction and binding affinity of T-cell epitopes with HLA-B7 were also investigated by molecular docking.

Result

Three distinct epitopes for vaccine design were predicted from the sequence of S protein. The potential B-cell epitope was KNHTSPDVDLG possessing the highest antigenicity score of 1.4039 among other B-cell epitopes. T-cell epitope for human MHC class I was VVVLSFELL with an antigenicity score of 1.0909 and binding ability to 29 MHC-I alleles. The predicted T-cell epitope for human MHC class II molecule was VVIGIVNNT with a corresponding 1.3063 antigenicity score, less digesting enzymes, and 7 MHC-II alleles binding ability. All these three peptides were predicted to be highly antigenic, non-allergenic, and non-toxic. Analyses of the physiochemical properties of these predicted epitopes indicate their stable nature for plausible vaccine design. Furthermore, molecular docking investigation between the MHC class-I epitopes and human HLA-B7 reflects the stable interaction with high affinity among them.

Conclusion

The present study posits three potential epitopes of S protein of SARS-CoV-2 predicted by immunoinformatic methods based on their immunogenic properties and interactions with the host counterpart that can facilitate the development of vaccine against SARS-CoV-2. This study can act as the springboard for the future development of the COVID-19 vaccine.

SUBMITTER: Ashik AI

PROVIDER: S-EPMC7472982 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundCoronavirus Disease (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 virus is evolving continuously. The omicron variant of SARS-CoV-2 has the highest mutation in its spike protein, thus making the presently available vaccine ineffective or reducing its efficiency. Furthermore, the majority of the vaccines are constructed using a spike protein sequence from wild-type SARS-CoV-2. This raises the possibility of the virus evolving to the point where the vaccine's effectiveness is completely lost, even after booster doses. The study aims to develop a predictive vaccine as well as the epitopes for the updating of the vaccine sequences of currently available vaccines. In this study, following the immunoinformatics approach, predictive vaccine construction was done with the help of epitopes present on spike proteins of wild-type, delta, and omicron variants that encompass the majority of variants and possible new variants that arise from the combination of circulating variants.ResultsThe vaccine that was constructed was stable and immunogenic. The vaccine was constructed with the help of 18 B-cell epitopes, 5 MHC class I epitopes, and 6 MHC class II epitopes. The epitope conservancy analysis suggests that the vaccine will work for the previously known variant of concern. The vaccine bound to TLR4, TLR2, B-cell receptor chains A and B, and ACE2 receptors with a z score of - 1.4, - 1.7, - 1.4, - 1.7, and - 1.4, respectively, with a cluster size of 121 highest for the ACE2 receptor and 46 lowest for B-cell receptor chain A. The C-ImmSim simulation results indicate that the vaccine is generating both humoral and cell-mediated responses at a sufficient level throughout the month upon injection of the vaccine as an antigen.ConclusionThe study's findings indicate that the vaccine was both stable and immunogenic, providing a sufficient level of immunity. Following experimental validation, the vaccine can be used, and the epitopes can be employed for therapeutic purposes such as antibody synthesis.Graphical abstractSupplementary informationThe online version contains supplementary material available at 10.1186/s43088-023-00341-4.

Project description:Introduction: The current incidence of the novel coronavirus disease has shown only small reductions of cases and has become a major public health challenge. Development of effective vaccines against the virus is still being encouraged such as multi-epitope vaccines designed from the components of SARS-CoV-2 including its spike, nucleocapsid and ORF1a proteins. Since the addition of adjuvants including HABA protein and L7/L12 ribosomal are considered helpful to increase the effectiveness of the designed vaccine, we proposed to design multiepitope vaccines by two different adjuvants. Methods: We used the IEDB server to predict BCL and TCL epitopes that were characterized using online tools including VaxiJen, AllPred and IL-10 Prediction. The selected epitopes were further constructed into multiepitope vaccines. We also added two different adjuvants to the vaccine components in order to increase the effectiveness of the vaccines. The 3D-structured vaccines were built using trRosetta. They were further docked with different Toll-like-receptors (TLR 3, 4 and 8) and the entry receptor of SARS-CoV-2, ACE2 using ClusPro, PatchDock and refined by FireDock. All structures were visualized by USCF Chimera and PyMOL. Results: In this study, we succeeded in designing two different candidate vaccines by the addition of HABA protein and L7/L12 ribosomal as adjuvants. The two vaccines were almost equally good in terms of their physicochemical properties and characteristics. Likewise, their strong interactions with TLR3 4, 8 and ACE2 show the lowest energy level of both was estimated at more than -1,000. Interactions of vaccines with ACE2 and TLRs are essential for activation of immune responses and production of antibodies. Conclusion: The two designed and constructed multiepitope vaccine have good characteristics and may have the potential to activate humoral and cellular immune responses against SARS-CoV-2. Further research is worth considering to confirm the findings of this study.