In silico T cell epitope identification for SARS-CoV-2: Progress and perspectives

Sohail, Muhammad Saqib; Ahmed, Syed Faraz; Quadeer, Ahmed Abdul; McKay, Matthew R.

doi:10.1016/j.addr.2021.01.007

Cited by 67 publications

(51 citation statements)

References 202 publications

(276 reference statements)

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“…Despite the numerous reverse vaccinology advances and all the bioinformatic tools that have been used in the analysis of the S glycoprotein and RBD domain sequences, few vaccines based on epitopes or immunogenic peptides have reached clinical phases ( Table 2 ) ( 112 , 125 , 126 ). Reverse vaccinology refers to a methodology that uses bioinformatic tools to identify genomic sequences and structures of infectious agents for the design of vaccines in silico ( 127 , 128 ).…”

Section: S Glycoprotein In Sars-cov-2 Vaccinesmentioning

confidence: 99%

SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

et al. 2021

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Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the complete S glycoprotein, its antigenic domains such as the receptor-binding domain (RBD) or short epitopes within the S glycoprotein. We also review and discuss the possible effectiveness of these vaccines against emerging SARS-CoV-2 variants.

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Section: S Glycoprotein In Sars-cov-2 Vaccinesmentioning

confidence: 99%

SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

et al. 2021

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“…Half of the studies have characterized T cell responses against the whole proteome, whereas the others have focused on responses mounted against subsets of SARS-CoV-2 proteins, typically involving the S and nucleocapsid [N] proteins. In the majority of cases, the T cell response was measured in blood samples of individuals against a set of peptides predicted by bioinformatics tools or earlier bioinformatics-based analyses 16,17,32 (reviewed in Sohail et al 46 ), whereas a few studies employed overlapping peptide pools spanning the SARS-CoV-2 proteome. All 18 studies reported optimal epitopes along with cognate HLA information.…”

Section: Resultsmentioning

confidence: 99%

Landscape of epitopes targeted by T cells in 852 individuals recovered from COVID-19: Meta-analysis, immunoprevalence, and web platform

Quadeer¹,

Ahmed²,

McKay³

2021

Cell Reports Medicine

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Knowledge of the epitopes of SARS-CoV-2 targeted by T cells in convalescent patients is important for understanding T cell immunity against COVID-19. This information can aid the development and assessment of COVID-19 vaccines, and inform novel diagnostic technologies. Here we provide a unified description and meta-analysis of SARS-CoV-2 T cell epitopes compiled from 18 studies of cohorts of convalescent COVID-19 patients (852 patients in total). Our analysis demonstrates the broad diversity of T cell epitopes that have been recorded for SARS-CoV-2. A large majority are seemingly unaffected by current variants of concern. We identify a set of 20 immunoprevalent epitopes that induced T cell responses in multiple cohorts and in a large fraction of tested patients. The landscape of SARS-CoV-2 T cell epitopes that we describe can help guide immunological studies, including those related to vaccines and diagnostics. A web-based platform has been developed to help complement these efforts.

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“…A number of recent studies have performed bioinformatic prediction of SARS-CoV-2 epitopes 17 . While these studies have identified viral peptide sequences that are likely immunogenic, they generally fail to account for mutational diversity in SARS-CoV-2 17,18 . Although our work does not directly predict variant neo-epitopes, it highlights the importance of epitopes that are recurrently mutated during viral evolution in response to immune pressure.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 vaccines dampen genomic diversity of SARS-CoV-2: Unvaccinated patients exhibit more antigenic mutational variance

Niesen

Anand

Silvert

et al. 2021

Preprint

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Variants of SARS-CoV-2 are evolving under a combination of immune selective pressure in infected hosts and natural genetic drift, raising a global alarm regarding the durability of COVID-19 vaccines. Here, we conducted longitudinal analysis over 1.8 million SARS-CoV-2 genomes from 183 countries or territories to capture vaccination-associated viral evolutionary patterns. To augment this macroscale analysis, we performed viral genome sequencing in 23 vaccine breakthrough COVID-19 patients and 30 unvaccinated COVID-19 patients for whom we also conducted machine-augmented curation of the electronic health records (EHRs). Strikingly, we find the diversity of the SARS-CoV-2 lineages is declining at the country-level with increased rate of mass vaccination (n = 25 countries, mean correlation coefficient = -0.72, S.D. = 0.20). Given that the COVID-19 vaccines leverage B-cell and T-cell epitopes, analysis of mutation rates shows neutralizing B-cell epitopes to be particularly more mutated than comparable amino acid clusters (4.3-fold, p < 0.001). Prospective validation of these macroscale evolutionary patterns using clinically annotated SARS-CoV-2 whole genome sequences confirms that vaccine breakthrough patients indeed harbor viruses with significantly lower diversity in known B cell epitopes compared to unvaccinated COVID-19 patients (2.3-fold, 95% C.I. 1.4-3.7). Incidentally, in these study cohorts, vaccinated breakthrough patients also displayed fewer COVID-associated complications and pre-existing conditions relative to unvaccinated COVID-19 patients. This study presents the first known evidence that COVID-19 vaccines are fundamentally restricting the evolutionary and antigenic escape pathways accessible to SARS-CoV-2. The societal benefit of mass vaccination may consequently go far beyond the widely reported mitigation of SARS-CoV-2 infection risk and amelioration of community transmission, to include stemming of rampant viral evolution.

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In silico T cell epitope identification for SARS-CoV-2: Progress and perspectives

Cited by 67 publications

References 202 publications

SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

Landscape of epitopes targeted by T cells in 852 individuals recovered from COVID-19: Meta-analysis, immunoprevalence, and web platform

COVID-19 vaccines dampen genomic diversity of SARS-CoV-2: Unvaccinated patients exhibit more antigenic mutational variance

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