In silico detection of SARS-CoV-2 specific B-cell epitopes and validation in ELISA for serological diagnosis of COVID-19

Phan, Isabelle; Subramanian, Sandhya; Kim, David; Carter, Lauren; King, Neil P.; Anishchenko, Ivan; Barrett, Lynn K.; Craig, Jonathan M.; Tillery, Logan; Shek, Roger; Harrington, Whitney E.; Koelle, David M.; Wald, Anna; Boonyaratanakornkit, Jim; Isoherranen, Nina; Greninger, Alexander L.; Jerome, Keith R.; Staker, Bart L.; Myler, Peter J.; Voorhis, Wesley C. Van

doi:10.1101/2020.05.22.111526

Cited by 9 publications

(12 citation statements)

References 29 publications

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“…The other possibility is the false positive PCR test. In our study as in (Phan, Subramanian et al 2020) detection of anti-RBD IgG yielded more reliable results than other tested antigens. Previously it was demonstrated that titers of anti-SARS-CoV-2 antibodies positively correlate with patient age (Wu, Wang et al 2020).…”

Section: Discussionsupporting

confidence: 66%

SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

Shomuradova

Vagida

Sheetikov

et al. 2020

Preprint

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Understanding the hallmarks of the adaptive immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed the antibody and T-cell reactivity in COVID-19 convalescent patients and healthy donors sampled both prior to and during the pandemic. The numbers of SARS- CoV-2-specific T cells were increased in healthy donors examined during COVID-19. Combined with the absence of symptoms and humoral response across that group, this finding suggests that some individuals might be protected by T-cell cross-reactivity. In convalescent patients we observed public and diverse T-cell response to SARS-CoV-2 epitopes, revealing T-cell receptor motifs with germline- encoded features. Bulk CD4+ and CD8+ T-cell responses to Spike glycoprotein were mediated by groups of homologous T-cell receptors, some of them shared across multiple donors. Overall, our results demonstrate that T-cell response to SARS-CoV-2, including the identified set of specific T-cell receptors, can serve as a useful biomarker for surveying viral exposure and immunity.

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Section: Discussionsupporting

confidence: 66%

SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

Shomuradova

Vagida

Sheetikov

et al. 2020

Preprint

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show abstract

“…Like Phan et al (2020), we found that detection of anti-RBD IgG yielded more reliable results than other tested antigens. On the other hand, although it was previously demonstrated that titers of anti-SARS-CoV-2 antibodies positively correlate with patient age (Wu et al, 2020a), we did not observe this pattern in our cohort.…”

Section: Discussionsupporting

confidence: 52%

SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors

et al. 2020

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Understanding the hallmarks of the immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed antibody and T cell reactivity in convalescent COVID-19 patients and healthy donors sampled both prior to and during the pandemic. Healthy donors examined during the pandemic exhibited increased numbers of SARS-CoV-2-specific T cells, but no humoral response. Their probable exposure to the virus resulted in either asymptomatic infection without antibody secretion, or activation of pre-existing immunity. In convalescent patients, we observed a public and diverse T cell response to SARS-CoV-2 epitopes, revealing T cell receptor (TCR) motifs with germline-encoded features. Bulk CD4 + and CD 8+ T cell responses to the spike glycoprotein were mediated by groups of homologous TCRs, some of them shared across multiple donors. Overall, our results demonstrate that the T cell response to SARS-CoV-2, including the identified set of TCRs, can serve as a useful biomarker for surveying antiviral immunity.

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“…In this study, we sought to overcome these limitations in study design and to more comprehensively examine the functional profiles of antigen-specific immune responses and their association with risk factors and clinical outcomes after COVID-19. We leveraged a large cohort of convalescent donors, including individuals recruited as candidate donors for convalescent plasma donation (29) in Seattle, WA, where SARS-CoV-2 community transmission was first described in the United States (30). We selected study participants that were either hospitalized (n=20) or not hospitalized (n=40) after matching for age, sex, ethnicity, and date of symptom onset.…”

Section: Introductionmentioning

confidence: 99%

Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2

Yu¹,

Fischinger²,

Smith³

et al. 2021

JCI Insight

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Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multi-parameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n=20) or not hospitalized (n=40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virusspecific CD4 T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4 T-cells and antibodies targeting the S1 domain of spike among subjects that were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.

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In silico detection of SARS-CoV-2 specific B-cell epitopes and validation in ELISA for serological diagnosis of COVID-19

Cited by 9 publications

References 29 publications

SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors

Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2

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