Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2

Qamar, Muhammad Tahir ul; Shahid, Farah; Aslam, Sadia; Ashfaq, Usman Ali; Aslam, Sidra; Fatima, Israr; Fareed, Muhammad Mazhar; Zohaib, Ali; Chen, Ling Ling

doi:10.1186/s40249-020-00752-w

Cited by 67 publications

(45 citation statements)

References 89 publications

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“…This offers proof of the practical significance of immunoinformatics. Similarly, various studies reported MEV constructs for SARS-CoV-2 using one or multiple proteins [ 33 , 34 , 88 – 95 ]. But none of them used all anti-genic proteins of SARS-CoV-2 both structure and non-structure collectively to screen a pool of conserved/overlapping epitopes to design a comprehensive MEV construct.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, they can trigger the versatile immune reactions by preparing cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL). IFN epitope server was used to calculate the IFN-γ inducing potential of selected epitopes using SVM hybrid algorithms along with Motif [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

“…The X-ray crystallographic structure of a common human allele (HLA-B7) was retrieved from protein data bank (PDB ID: 3VCL). Molecular docking was performed using same protocol of our previously published studies [ 19 – 21 , 34 ]. To visualize the docked complexes and draw figures, the PyMOL educational version was used [ 56 ].…”

Section: Methodsmentioning

confidence: 99%

“…MEVs are more advantageous in comparison with single-epitope vaccines or conventional vaccines, due to their cost effective, time saving, stability and specificity properties. Additionally, they are believed to induce significant humoral and cellular immune responses, simultaneously because of the presence of T-cell as well as B-cell epitopes [ 33 , 34 ]. As MEVs consist of adjuvants, they believed to developed long-lasting immune responses and increased immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

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Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches

et al. 2020

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Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus 2 (SARS-COV-2) is a significant threat to global health security. Till date, no completely effective drug or vaccine is available to cure COVID-19. Therefore, an effective vaccine against SARS-COV-2 is crucially needed. This study was conducted to design an effective multiepitope based vaccine (MEV) against SARS-COV-2. Seven highly antigenic proteins of SARS-COV-2 were selected as targets and different epitopes (B-cell and T-cell) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected epitopes indicated significant interactions with the HLA-binding alleles and 99.93% coverage of the world’s population. Hence, 505 amino acids long MEV was designed by connecting 16 MHC class I and eleven MHC class II epitopes with suitable linkers and adjuvant. MEV construct was non-allergenic, antigenic, stable and flexible. Furthermore, molecular docking followed by molecular dynamics (MD) simulation analyses, demonstrated a stable and strong binding affinity of MEV with human pathogenic toll-like receptors (TLR), TLR3 and TLR8. Finally, MEV codons were optimized for its in silico cloning into Escherichia coli K-12 system, to ensure its increased expression. Designed MEV in present study could be a potential candidate for further vaccine production process against COVID-19. However, to ensure its safety and immunogenic profile, the proposed MEV needs to be experimentally validated.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches

et al. 2020

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“…These results highlight the importance of pre-existing and induced SARS-CoV-2-specific CD8+ and CD4+ T cell responses for immune protection in mild SARS-CoV-2 infection. Since then, studies suggested the inclusion of specific peptides to elicit T cell response in vaccine design and in silico analysis of SARS-CoV-2 proteins has detected candidate epitopes specific for protective T CD4+ or CD8+ and B responses with low risks of allergy or autoimmunity (17)(18)(19)(20) . In fact, approved vaccines induce T cell response in addition to the production of neutralizing antibodies for immunization against SARS-CoV-2 (21)(22)(23) .…”

Section: Introductionmentioning

confidence: 99%

New SARS-CoV-2 lineages could evade CD8+ T-cells response

Pretti

Galvani

Farias

et al. 2021

Preprint

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Background: Many SARS-CoV-2 variants of concern have emerged since the Covid-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antibody recognition. However, not enough attention has been given to pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses during the natural course of infection by new lineages. Methods: In this work, we investigated the SARS-CoV-2-specific CD8+ T cell epitopes from the main variants of concern and the potential of associated mutations to trigger or hinder CD8+ T-cells response. We also estimated the population's coverage of these different lineages, considering peptide binding predictions to class I HLA alleles from 29 countries to investigate differences in the fraction of individuals expected to respond to a given epitope set from new and previous lineages. Results: We observed a lower populational coverage for 20B/S.484K (P2 lineage) in contrast to an increased coverage found for 20H/501Y.V2 (B.1.351 Lineage) and 20J/501Y.V3 (P1 lineage) compared to a reference lineage. Moreover, mutations such as Spike N501Y and Nucleocapsid T205I were predicted to have an overall higher affinity through HLA-I than the reference sequence. Conclusions: In summary, the data in this work provided evidence for the existence of potentially immunogenic and conserved epitopes across new SARS-CoV-2 variants, but also highlights the reduced populational's coverage for the Brazilian lineage P.1, suggesting its potential to evade from CD8+ T-cell responses. Our results also may guide efforts to characterize and validate relevant peptides to trigger CD8+ T-cell responses, and design new universal T-cell-inducing vaccine candidates that minimize detrimental effects of viral diversification and at the same time induce responses to a broad human population.

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Physicochemical properties of SARS‐CoV‐2 for drug targeting, virus inactivation and attenuation, vaccine formulation and quality control

et al. 2020

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The material properties of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its proteins are discussed. We review the viral structure, size, rigidity, lipophilicity, isoelectric point, buoyant density and centrifugation conditions, stability against pH, temperature, UV light, gamma radiation, and susceptibility to various chemical agents including solvents and detergents. Possible inactivation, downstream, and formulation conditions are given including suitable buffers and some first ideas for quality-control methods. This information supports vaccine development and discussion with competent authorities during vaccine approval and is certainly related to drug-targeting strategies and hygienics. Several instructive tables are given, including the pI and grand average of hydropathicity (GRAVY) of SARS-CoV-1 and-2 proteins in comparison. SARS-CoV-1 and SARS-CoV-2 are similar in many regards, so information can often be derived. Both are unusually stable, but sensitive at their lipophilic membranes. However, since seemingly small differences can have strong effects, for example, on immunologically relevant epitope settings, unevaluated knowledge transfer from SARS-CoV-1 to SARS-CoV-2 cannot be advised. Published knowledge regarding downstream processes, formulations and quality assuring methods is, as yet, limited. However, standard approaches employed for other viruses and vaccines seem to be feasible including virus inactivation, centrifugation conditions, and the use of adjuvants.

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Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2

Cited by 67 publications

References 89 publications

Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches

Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches

New SARS-CoV-2 lineages could evade CD8+ T-cells response

Physicochemical properties of SARS‐CoV‐2 for drug targeting, virus inactivation and attenuation, vaccine formulation and quality control

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