Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences

Zaheer, Tahreem; Waseem, Maaz; Waqar, Walifa; Dar, Hamza Arshad; Shehroz, Muhammad; Naz, Kanwal; Ishaq, Zaara; Ahmad, Tahir; Ullah, Nimat; Bakhtiar, Syeda Marriam; Muhammad, Syed Aun; Ali, Amjad

doi:10.7717/peerj.9541

Cited by 20 publications

(17 citation statements)

References 78 publications

(102 reference statements)

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“…The SARS-CoV-2 S protein is regarded as a leading target in vaccine development ( Poh et al, 2020 , Samrat et al, 2020 , Pillay, 2020 ). Previous studies reported the identification of putative T cell epitopes using in silico tools ( Crooke et al, 2020 , Abraham Peele et al, 2020 , Jakhar et al, 2020 , Zaheer et al, 2020 ) and evaluated T cell responses using COVID-19 patients’ immune cells stimulated with SARS-CoV-2 S protein or mixed peptides (rather than discrete, individual peptide motifs) ( Grifoni et al, 2020 , Braun et al, 2020 ). Thus, we set out to identify virus-specific T cell epitopes using overlapping peptide stimulation in memory T cells from COVID-19-recovered patients, followed by ELISpot assay.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

et al. 2021

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The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to public health. An explicit investigation of COVID-19 immune responses, particularly the host immunity in recovered subjects, will lay a foundation for the rational design of therapeutics and/or vaccines against future coronaviral outbreaks. Here, we examined virus-specific T cell responses and identified T cell epitopes using peptides spanning SARS-CoV-2 structural proteins. These peptides were used to stimulate peripheral blood mononuclear cells (PBMCs) derived from COVID-19-recovered subjects, followed by an analysis of IFN-γ-secreting T cells by enzyme-linked immunosorbent spot (ELISpot). We also evaluated virus-specific CD4 or CD8 T cell activation by flow cytometry assay. By screening 52 matrix pools (comprised of 315 peptides) of the spike (S) glycoprotein and 21 matrix pools (comprised of 102 peptides) spanning the nucleocapsid (N) protein, we identified 28 peptides from S protein and 5 peptides from N protein as immunodominant epitopes. The immunogenicity of these epitopes was confirmed by a second ELISpot using single peptide stimulation in memory T cells, and they were mapped by HLA restrictions. Notably, SARS-CoV-2 specific T cell responses positively correlated with B cell IgG and neutralizing antibody responses to the receptor-binding domain (RBD) of the S protein. Our results demonstrate that defined levels of SARS-CoV-2 specific T cell responses are generated in some, but not all, COVID-19-recovered subjects, fostering hope for the protection of a proportion of COVID-19-exposed individuals against reinfection. These results also suggest that these virus-specific T cell responses may induce protective immunity in unexposed individuals upon vaccination, using vaccines generated based on the immune epitopes identified in this study. However, SARS-CoV-2 S and N peptides are not potently immunogenic, and none of the single peptides could universally induce robust T cell responses, suggesting the necessity of using a multi-epitope strategy for COVID-19 vaccine design.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

et al. 2021

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“…Antigenicity, Allergenicity, Cell Localization, and Immune System Response. The antigenicity scores of the polyvalent are constructed by Vaxijen 2.0 (threshold value: 0.5), Antigenpro (threshold value: 0.3) [46], and Secret-AAR [40]. Our construct showed an antigenicity score above the threshold value and considered antigenic.…”

Section: Molecular Modeling Of Epitopesmentioning

confidence: 99%

Designing of Potential Polyvalent Vaccine Model for Respiratory Syncytial Virus by System Level Immunoinformatics Approaches

Naqvi

Yasmeen

Ismail

et al. 2021

BioMed Research International

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Background. Respiratory syncytial virus (RSV) infection is a public health epidemic, leading to around 3 million hospitalization and about 66,000 deaths each year. It is a life-threatening condition exclusive to children with no effective treatment. Methods. In this study, we used system-level and vaccinomics approaches to design a polyvalent vaccine for RSV, which could stimulate the immune components of the host to manage this infection. Our framework involves data accession, antigenicity and subcellular localization analysis, T cell epitope prediction, proteasomal and conservancy evaluation, host-pathogen-protein interactions, pathway studies, and in silico binding affinity analysis. Results. We found glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH) of RSV as potential vaccine candidates. Of these proteins (G, F, and SH), we found 9 epitopes for multiple alleles of MHC classes I and II bear significant binding affinity. These potential epitopes were linked to form a polyvalent construct using AAY, GPGPG linkers, and cholera toxin B adjuvant at N-terminal with a 23.9 kDa molecular weight of 224 amino acid residues. The final construct was a stable, immunogenic, and nonallergenic protein containing cleavage sites, TAP transport efficiency, posttranslation shifts, and CTL epitopes. The molecular docking indicated the optimum binding affinity of RSV polyvalent construct with MHC molecules (-12.49 and -10.48 kcal/mol for MHC classes I and II, respectively). This interaction showed that a polyvalent construct could manage and control this disease. Conclusion. Our vaccinomics and system-level investigation could be appropriate to trigger the host immune system to prevent RSV infection.

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“…Further, studies following a combinatorial approach (H.-Z. Zaheer et al, 2020) are also expected to miss some of the epitopes reported in this study. It may however be noted that like most previous studies, the current study refrained from predicting potential B-cell epitopes, due to the computational complexities involved in the process and may be considered a limitation of this exercise.…”

Section: Discussionmentioning

confidence: 90%

Does immune recognition of SARS-CoV2 epitopes vary between different ethnic groups?

Bose

Pant

Pinna

et al. 2021

Preprint

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The SARS-CoV2 mediated Covid-19 pandemic has impacted humankind at an unprecedented scale. While substantial research efforts have focused towards understand the mechanisms of viral infection and developing vaccines/ therapeutics, factors affecting the susceptibility to SARS-CoV2 infection and manifestation of Covid-19 remain less explored. Given that the Human Leukocyte Antigen (HLA) system is known to vary among ethnic populations, it is likely to affect the recognition of the virus, and in turn, the susceptibility to Covid-19. To understand this, we used bioinformatic tools to probe all SARS-CoV2 peptides which could elicit T-cell response in humans. We also tried to answer the intriguing question of whether these potential epitopes were equally immunogenic across ethnicities, by studying the distribution of HLA alleles among different populations and their share of cognate epitopes. We provide evidence that the newer mutations in SARS-CoV2 are unlikely to alter the T-cell mediated immunogenic responses among the studied ethnic populations. The work presented herein is expected to bolster our understanding of the pandemic, by providing insights into differential immunological response of ethnic populations to the virus as well as by gauging the possible effects of mutations in SARS-CoV2 on efficacy of potential epitope-based vaccines through evaluating ~40000 viral genomes.

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Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences

Cited by 20 publications

References 78 publications

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects

Designing of Potential Polyvalent Vaccine Model for Respiratory Syncytial Virus by System Level Immunoinformatics Approaches

Does immune recognition of SARS-CoV2 epitopes vary between different ethnic groups?

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