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Potential CD8+ T Cell Cross-Reactivity Against SARS-CoV-2 Conferred by Other Coronavirus Strains.

ABSTRACT: While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory to related pathogens cross-reactive against SARS-CoV-2 can influence the disease outcome in COVID-19. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated an in silico map of public and private CD8+ T cell epitopes between coronaviruses. We observed 794 predicted SARS-CoV-2 epitopes of which 52% were private and 48% were public. Ninety-nine percent of the public epitopes were shared with SARS-CoV and 5.4% were shared with either one of four common coronaviruses, 229E, HKU1, NL63, and OC43. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB, and found only a small number of peptides with limited potential for cross-reactivity between the two virus families. We believe our comprehensive in silico profile of private and public epitopes across coronaviruses would facilitate design of vaccines, and provide insights into the presence of pre-existing coronavirus-specific memory CD8+ T cells that may influence immune responses against SARS-CoV-2.

SUBMITTER: Lee CH

PROVIDER: S-EPMC7676914 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Potential CD8+ T Cell Cross-Reactivity Against SARS-CoV-2 Conferred by Other Coronavirus Strains.

Lee Chloe H CH Pinho Mariana Pereira MP Buckley Paul R PR Woodhouse Isaac B IB Ogg Graham G Simmons Alison A Napolitani Giorgio G Koohy Hashem H

Frontiers in immunology 20201105

While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory to related pathogens cross-reactive against SARS-CoV-2 can influence the disease outcome in COVID-19. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated an <i>in ...[more]

PMID: 33250893

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Project description:Abstract Background The impact of COVID-19 has been profound with >170,000,000 confirmed cases worldwide and emerging variants being a cause of global concern. Defects in T-cell function and trafficking have been described among those with severe illness, and immunodeficiency is a risk factor for persistent viral shedding and prolonged symptoms. Because of our prior clinical data demonstrating that allogeneic, off-the-shelf virus-specific T cells (VSTs) can safely and effectively treat viral infections, we investigated the feasibility of targeting COVID-19 using banked, SARS-CoV-2-specific VSTs. Methods We first screened PBMCs from convalescent individuals against 18 structural and non-structural/accessory (NSPs/APs) SARS-CoV-2 proteins and identified 5 [Spike (S), Membrane (M), Nucleoprotein (N), NSP4, and AP7a] as immunodominant which were then advanced to our VST production process. Results Using overlapping peptide libraries spanning these antigens as a stimulus, we achieved a mean 7.6±0.9 fold expansion (n=13) of VSTs (96±0.5%), with a mixture of cytotoxic (CD8+) and helper (CD4+) T cells that expressed activation and central/effector memory markers. These VSTs were potent, Th1-polarized and polyfunctional, producing IFNγ, TNFα, GM-CSF and Granzyme B. Moreover, the VSTs were able to kill pepmix-loaded autologous targets with no evidence of auto- or alloreactivity, attesting to their virus selectivity and safety for clinical use (Figure 1). Finally, though initially generated against the reference strain NC_045512.2 (Wuhan), these VSTs were able to recognize other clinically important variants including B1.1.7 (UK), B1.351 (South Africa) and P1 (Brazil). This demonstrates the cross-reactive potential of these polyclonal and diverse VSTs, which were developed to provide potent antiviral effects and minimize the risk of immune escape due to sequence variation. Figure 1: SARS-CoV-2 Specific T cells Have Demonstrated Selective Cytolytic Activity against SARS-CoV-2 While Leaving Non-Virus Infected Targets Intact. Conclusion In conclusion, it is feasible to generate polyclonal SARS-CoV-2 VSTs that provide coverage against variant strains using GMP-compliant manufacturing methodologies. We have advanced this product to the bedside for administration in a Phase I, randomized clinical trial [VSTs+ standard of care (SOC) vs SOC] in high-risk patients hospitalized with COVID-19 (NCT04401410). Disclosures Spyridoula Vasileiou, PhD, AlloVir (Consultant) Manik Kuvalekar, MSc, AlloVir (Consultant) Aster Workineh, MSc, AlloVir (Employee) Ayumi Watanabe, BSc, AlloVir (Consultant) Yovana Velazquez, BSc, AlloVir (Consultant) Helen Elisabeth Heslop, MD, AlloVir (Shareholder)Cell Medica (Grant/Research Support)Gilead Sciences (Consultant)Kiadis Pharma (Consultant)Marker Therapeutics (Consultant, Shareholder)Mesoblast (Consultant)Novartis (Consultant)PACT Pharma (Consultant)Tessa Therapeutics (Consultant, Research Grant or Support) Premal Lulla, MD, Johnson & Johnson (Shareholder) Ann Marie Leen, PhD, AlloVIr (Consultant, Shareholder)Marker Therapeutics (Consultant, Shareholder)

Dataset Information

Potential CD8+ T Cell Cross-Reactivity Against SARS-CoV-2 Conferred by Other Coronavirus Strains.

Publications

Potential CD8+ T Cell Cross-Reactivity Against SARS-CoV-2 Conferred by Other Coronavirus Strains.

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