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Article ; Online: An update on studies characterizing adaptive immune responses in SARS-CoV-2 infection and COVID-19 vaccination.

da Silva Antunes, Ricardo / Grifoni, Alba / Frazier, April / Weiskopf, Daniela / Sette, Alessandro

2023 Volume 35, Issue 8, Page(s) 353–359

Abstract: In this brief opinion piece, we highlight our studies characterizing adaptive SARS-CoV-2 immune responses in infection and vaccination, and the ability of SARS-CoV-2-specific T cells to recognize emerging variants of concern, and the role of pre-existing ...

Abstract	In this brief opinion piece, we highlight our studies characterizing adaptive SARS-CoV-2 immune responses in infection and vaccination, and the ability of SARS-CoV-2-specific T cells to recognize emerging variants of concern, and the role of pre-existing cross-reactive T cells. In the context of the debate on correlates of protection, the pandemic's progression in the past 3 years underlined the need to consider how different adaptive immune responses might differentially contribute to protection from SARS-CoV-2 infection versus COVID-19 disease. Lastly, we discuss how cross-reactive T cell responses may be useful in generating a broad adaptive immunity, recognizing different variants and viral families. Considering vaccines with broadly conserved antigens could improve preparedness for future infectious disease outbreaks.
MeSH term(s)	Humans ; COVID-19/prevention & control ; COVID-19 Vaccines ; SARS-CoV-2 ; Vaccination ; Adaptive Immunity
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2023-05-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxad014
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Article ; Online: Investigating viral and autoimmune T cell responses associated with post-acute sequelae of COVID-19.

Williams, Gregory P / Yu, Esther Dawen / Shapiro, Kendra / Wang, Eric / Freuchet, Antoine / Frazier, April / Lindestam Arlehamn, Cecilia S / Sette, Alessandro / da Silva Antunes, Ricardo

Human immunology

2024 , Page(s) 110770

Abstract: Post-acute sequelae of COVID-19 (PASC), or Long COVID, is a chronic condition following acute SARS-CoV-2 infection. Symptoms include exertion fatigue, respiratory issues, myalgia, and neurological manifestations such as 'brain fog,' posing concern for ... ...

Abstract	Post-acute sequelae of COVID-19 (PASC), or Long COVID, is a chronic condition following acute SARS-CoV-2 infection. Symptoms include exertion fatigue, respiratory issues, myalgia, and neurological manifestations such as 'brain fog,' posing concern for their debilitating nature and potential role in other neurological disorders. However, the underlying potential pathogenic mechanisms of the neurological complications of PASC is largely unknown. Herein, we investigated differences in antigen-specific T cell responses from the peripheral blood towards SARS-CoV-2, latent viruses, or neuronal antigens in 14 PASC individuals with neurological manifestations (PASC-N) versus 22 individuals fully recovered from COVID-19. We employed Activation Induced Marker (AIM), ICS and FluoroSpot assays to determine the specificity and magnitude of CD4
Language	English
Publishing date	2024-03-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2024.110770
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Article: PINK1 is a target of T cell responses in Parkinson's disease.

Williams, Gregory P / Michaelis, Tanner / Lima-Junior, João Rodrigues / Frazier, April / Tran, Ngan K / Phillips, Elizabeth J / Mallal, Simon A / Litvan, Irene / Goldman, Jennifer G / Alcalay, Roy N / Sidney, John / Sulzer, David / Sette, Alessandro / Lindestam Arlehamn, Cecilia S

bioRxiv : the preprint server for biology

2024

Abstract: Parkinson's disease (PD) is associated with autoimmune T cells that recognize the protein alpha-synuclein in a subset of individuals. Multiple neuroantigens are targets of autoinflammatory T cells in classical central nervous system autoimmune diseases ... ...

Abstract	Parkinson's disease (PD) is associated with autoimmune T cells that recognize the protein alpha-synuclein in a subset of individuals. Multiple neuroantigens are targets of autoinflammatory T cells in classical central nervous system autoimmune diseases such as multiple sclerosis (MS). Here, we explored whether additional autoantigenic targets of T cells in PD. We generated 15-mer peptide pools spanning several PD-related proteins implicated in PD pathology, including GBA, SOD1, PINK1, parkin, OGDH, and LRRK2. Cytokine production (IFNγ, IL-5, IL-10) against these proteins was measured using a fluorospot assay and PBMCs from patients with PD and age-matched healthy controls. This approach identified unique epitopes and their HLA restriction from the mitochondrial-associated protein PINK1, a regulator of mitochondrial stability, as an autoantigen targeted by T cells. The T cell reactivity was predominantly found in male patients with PD, which may contribute to the heterogeneity of PD. Identifying and characterizing PINK1 and other autoinflammatory targets may lead to antigen-specific diagnostics, progression markers, and/or novel therapeutic strategies for PD.
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.09.579465
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Article: Targets and cross-reactivity of human T cell recognition of Common Cold Coronaviruses.

Tarke, Alison / Zhang, Yun / Methot, Nils / Narowski, Tara M / Phillips, Elizabeth / Mallal, Simon / Frazier, April / Filaci, Gilberto / Weiskopf, Daniela / Dan, Jennifer M / Premkumar, Lakshmanane / Scheuermann, Richard H / Sette, Alessandro / Grifoni, Alba

bioRxiv : the preprint server for biology

2023

Abstract: The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, ... ...

Abstract	The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, including sarbecoCoV (SARS-CoV and SARS-CoV-2) and merbecoCoV (MERS-CoV). It is therefore warranted to explore pan-CoV vaccine concepts, to provide adaptive immune protection against new potential CoV outbreaks, particularly in the context of betaCoV sub lineages. To explore the feasibility of eliciting CD4
Language	English
Publishing date	2023-01-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.04.522794
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Article ; Online: Targets and cross-reactivity of human T cell recognition of common cold coronaviruses.

Cell reports. Medicine

2023 Volume 4, Issue 6, Page(s) 101088

Abstract: The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and ... ...

Abstract	The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and Beta (OC43) common cold CoVs (CCCs) in pre-pandemic samples. S, N, M, and nsp3 antigens are immunodominant, as shown for severe acute respiratory syndrome 2 (SARS2), while nsp2 and nsp12 are Alpha or Beta specific. We further identify 78 OC43- and 87 NL63-specific epitopes, and, for a subset of those, we assess the T cell capability to cross-recognize sequences from representative viruses belonging to AlphaCoV, sarbecoCoV, and Beta-non-sarbecoCoV groups. We find T cell cross-reactivity within the Alpha and Beta groups, in 89% of the instances associated with sequence conservation >67%. However, despite conservation, limited cross-reactivity is observed for sarbecoCoV, indicating that previous CoV exposure is a contributing factor in determining cross-reactivity. Overall, these results provide critical insights in developing future pan-CoV vaccines.
MeSH term(s)	Humans ; Common Cold ; T-Lymphocytes ; COVID-19 ; SARS-CoV-2 ; Cross Reactions
Language	English
Publishing date	2023-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.101088
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Article ; Online: Identification of cow milk epitopes to characterize and quantify disease-specific T cells in allergic children.

Lewis, Sloan A / Sutherland, Aaron / Soldevila, Ferran / Westernberg, Luise / Aoki, Minori / Frazier, April / Maiche, Synaida / Erlewyn-Lajeunesse, Mich / Arshad, Hasan / Leonard, Stephanie / Laubach, Susan / Dantzer, Jennifer A / Wood, Robert A / Sette, Alessandro / Seumois, Gregory / Vijayanand, Pandurangan / Peters, Bjoern

The Journal of allergy and clinical immunology

2023 Volume 152, Issue 5, Page(s) 1196–1209

Abstract: Background: Cow milk (CM) allergy is the most prevalent food allergy in young children in the United States and Great Britain. Current diagnostic tests are either unreliable (IgE test and skin prick test) or resource-intensive with risks (food ... ...

Abstract	Background: Cow milk (CM) allergy is the most prevalent food allergy in young children in the United States and Great Britain. Current diagnostic tests are either unreliable (IgE test and skin prick test) or resource-intensive with risks (food challenges). Objective: We sought to determine whether allergen-specific T cells in CM-allergic (CMA) patients have a distinct quality and/or quantity that could potentially be used as a diagnostic marker. Methods: Using PBMCs from 147 food-allergic pediatric subjects, we mapped T-cell responses to a set of reactive epitopes in CM that we compiled in a peptide pool. This pool induced cytokine responses in in vitro cultured cells distinguishing subjects with CMA from subjects without CMA. We further used the pool to isolate and characterize antigen-specific CD4 memory T cells using flow cytometry and single-cell RNA/TCR sequencing assays. Results: We detected significant changes in the transcriptional program and clonality of CM antigen-specific (CM+) T cells elicited by the pool in subjects with CMA versus subjects without CMA ex vivo. CM+ T cells from subjects with CMA had increased percentages of FOXP3 Conclusions: Overall, these findings suggest that there are several differences in the phenotypes of CM+ T cells with CM allergy and that the increase in CM+ FOXP3
MeSH term(s)	Animals ; Cattle ; Female ; Child ; Humans ; Child, Preschool ; Milk ; Epitopes ; Allergens ; Cytokines/metabolism ; Food Hypersensitivity/complications ; Milk Hypersensitivity/diagnosis ; Milk Hypersensitivity/complications ; Forkhead Transcription Factors/metabolism
Chemical Substances	Epitopes ; Allergens ; Cytokines ; Forkhead Transcription Factors
Language	English
Publishing date	2023-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.07.020
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Article: Genome-wide characterization of T cell responses to

da Silva Antunes, Ricardo / Garrigan, Emily / Quiambao, Lorenzo G / Dhanda, Sandeep Kumar / Marrama, Daniel / Westernberg, Luise / Wang, Eric / Sutherland, Aaron / Armstrong, Sandra K / Brickman, Timothy J / Sidney, John / Frazier, April / Merkel, Tod / Peters, Bjoern / Sette, Alessandro

bioRxiv : the preprint server for biology

2023

Abstract: The incidence of whooping cough (pertussis), the respiratory disease caused ... ...

Abstract	The incidence of whooping cough (pertussis), the respiratory disease caused by
Language	English
Publishing date	2023-03-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.24.534182
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Article ; Online: T cell reactivity to Bordetella pertussis is highly diverse regardless of childhood vaccination.

da Silva Antunes, Ricardo / Garrigan, Emily / Quiambao, Lorenzo G / Dhanda, Sandeep Kumar / Marrama, Daniel / Westernberg, Luise / Wang, Eric / Abawi, Adam / Sutherland, Aaron / Armstrong, Sandra K / Brickman, Timothy J / Sidney, John / Frazier, April / Merkel, Tod J / Peters, Bjoern / Sette, Alessandro

Cell host & microbe

2023 Volume 31, Issue 8, Page(s) 1404–1416.e4

Abstract: The incidence of whooping cough due to Bordetella pertussis (BP) infections has increased recently. It is believed that the shift from whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines may be contributing to this rise. While T cells ...

Abstract	The incidence of whooping cough due to Bordetella pertussis (BP) infections has increased recently. It is believed that the shift from whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines may be contributing to this rise. While T cells are key in controlling and preventing disease, nearly all knowledge relates to antigens in aP vaccines. A whole-genome mapping of human BP-specific CD4+ T cell responses was performed in healthy vaccinated adults and revealed unexpected broad reactivity to hundreds of antigens. The overall pattern and magnitude of T cell responses to aP and non-aP vaccine antigens are similar regardless of childhood vaccination, suggesting that asymptomatic infections drive the pattern of T cell reactivity in adults. Lastly, lack of Th1/Th2 polarization to non-aP vaccine antigens suggests these antigens have the potential to counteract aP vaccination Th2 bias. These findings enhance our insights into human T cell responses to BP and identify potential targets for next-generation pertussis vaccines.
MeSH term(s)	Adult ; Humans ; Bordetella pertussis ; Whooping Cough/prevention & control ; Immunization, Secondary ; Pertussis Vaccine ; Vaccination
Chemical Substances	Pertussis Vaccine
Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2023.06.015
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Article ; Online: Ex vivo

Yu, Esther Dawen / Wang, Eric / Garrigan, Emily / Sutherland, Aaron / Khalil, Natalie / Kearns, Kendall / Pham, John / Schulten, Veronique / Peters, Bjoern / Frazier, April / Sette, Alessandro / da Silva Antunes, Ricardo

Cell reports methods

2022 Volume 2, Issue 12, Page(s) 100350

Abstract: Gamma-delta (γδ) T cells contribute to the pathology of many immune-related diseases; however, ... ...

Abstract	Gamma-delta (γδ) T cells contribute to the pathology of many immune-related diseases; however, no
MeSH term(s)	Humans ; Animals ; Mice ; Allergens ; Hypersensitivity ; Cytokines/metabolism ; Intraepithelial Lymphocytes/metabolism
Chemical Substances	Allergens ; Cytokines
Language	English
Publishing date	2022-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2667-2375
ISSN (online)	2667-2375
DOI	10.1016/j.crmeth.2022.100350
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Article ; Online: Immunological memory to common cold coronaviruses assessed longitudinally over a three-year period pre-COVID19 pandemic.

Yu, Esther Dawen / Narowski, Tara M / Wang, Eric / Garrigan, Emily / Mateus, Jose / Frazier, April / Weiskopf, Daniela / Grifoni, Alba / Premkumar, Lakshmanane / da Silva Antunes, Ricardo / Sette, Alessandro

Cell host & microbe

2022 Volume 30, Issue 9, Page(s) 1269–1278.e4

Abstract: The immune memory to common cold coronaviruses (CCCs) influences SARS-CoV-2 infection outcome, and understanding its effect is crucial for pan-coronavirus vaccine development. We performed a longitudinal analysis of pre-COVID19-pandemic samples from 2016- ...

Abstract	The immune memory to common cold coronaviruses (CCCs) influences SARS-CoV-2 infection outcome, and understanding its effect is crucial for pan-coronavirus vaccine development. We performed a longitudinal analysis of pre-COVID19-pandemic samples from 2016-2019 in young adults and assessed CCC-specific CD4+ T cell and antibody responses. Notably, CCC responses were commonly detected with comparable frequencies as with other common antigens and were sustained over time. CCC-specific CD4+ T cell responses were associated with low HLA-DR+CD38+ signals, and their magnitude did not correlate with yearly CCC infection prevalence. Similarly, CCC-specific and spike RBD-specific IgG responses were stable in time. Finally, high CCC-specific CD4+ T cell reactivity, but not antibody titers, was associated with pre-existing SARS-CoV-2 immunity. These results provide a valuable reference for understanding the immune response to endemic coronaviruses and suggest that steady and sustained CCC responses are likely from a stable pool of memory CD4+ T cells due to repeated earlier exposures and possibly occasional reinfections.
MeSH term(s)	Antibodies, Viral ; COVID-19 ; COVID-19 Vaccines ; Common Cold/epidemiology ; Humans ; Immunoglobulin G ; Immunologic Memory ; Pandemics ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2022.07.012
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