High titre neutralizing antibodies in response to SARS–CoV–2 infection require RBD–specific CD4 T cells that include proliferative memory cells

Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden. We have investigated the association between memory CD4 and CD8 T cells and levels of neutrali...

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Vydané v:	Frontiers in immunology Ročník 13; s. 1032911
Hlavní autori:	Phetsouphanh, Chansavath, Khoo, Weng Hua, Jackson, Katherine, Klemm, Vera, Howe, Annett, Aggarwal, Anupriya, Akerman, Anouschka, Milogiannakis, Vanessa, Stella, Alberto Ospina, Rouet, Romain, Schofield, Peter, Faulks, Megan L., Law, Hannah, Danwilai, Thidarat, Starr, Mitchell, Munier, C. Mee Ling, Christ, Daniel, Singh, Mandeep, Croucher, Peter I., Brilot-Turville, Fabienne, Turville, Stuart, Phan, Tri Giang, Dore, Gregory J., Darley, David, Cunningham, Philip, Matthews, Gail V., Kelleher, Anthony D., Zaunders, John J.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Switzerland Frontiers Media S.A 05.12.2022
Predmet:	Antibodies, Neutralizing CD4 function CD4 T cells CD4-Positive T-Lymphocytes COVID-19 Epitopes, T-Lymphocyte Humans Immunology neutralizing antibodies proliferation SARS-CoV-2 neutralizing antibodies SARS-CoV-2 CD4 T cells CD4 function proliferation
ISSN:	1664-3224, 1664-3224
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Abstract	Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden. We have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects. Higher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorously . Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres. Our results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines.
AbstractList	BackgroundLong-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden.MethodsWe have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects.FindingsHigher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorously in vitro. Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres.InterpretationOur results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines. Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden. We have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects. Higher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorously . Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres. Our results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines. Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden.BackgroundLong-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden.We have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects.MethodsWe have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects.Higher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorously in vitro. Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres.FindingsHigher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorously in vitro. Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres.Our results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines.InterpretationOur results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines.
Author	Schofield, Peter Kelleher, Anthony D. Faulks, Megan L. Howe, Annett Rouet, Romain Munier, C. Mee Ling Darley, David Aggarwal, Anupriya Turville, Stuart Zaunders, John J. Akerman, Anouschka Cunningham, Philip Brilot-Turville, Fabienne Law, Hannah Milogiannakis, Vanessa Danwilai, Thidarat Dore, Gregory J. Phetsouphanh, Chansavath Croucher, Peter I. Phan, Tri Giang Christ, Daniel Khoo, Weng Hua Klemm, Vera Matthews, Gail V. Singh, Mandeep Jackson, Katherine Stella, Alberto Ospina Starr, Mitchell
AuthorAffiliation	2 Garvan Institute of Medical Research , Sydney, NSW , Australia 7 Department of Infectious Diseases, St. Vincent's Hospital , Sydney, NSW , Australia 3 St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales (UNSW) Sydney , Sydney, NSW , Australia 4 NSW State Reference Laboratory for HIV, St. Vincent’s Centre for Applied Medical Research , Sydney, NSW , Australia 1 Kirby Institute, University of New South Wales (UNSW) , Sydney, NSW , Australia 6 Sydney Institute for Infectious Diseases, The University of Sydney , Sydney, NSW , Australia 5 Brain and Mind Centre, Children’s Hospital at Westmead, University of Sydney , Sydney, NSW , Australia 8 Department of Immunology, St Vincent's Hospital , Sydney, NSW , Australia
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/36544780$$D View this record in MEDLINE/PubMed
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Cites_doi	10.1038/s41577-020-00451-5 10.1016/j.cell.2019.05.031 10.1038/s41591-021-01377-8 10.1038/s41467-022-28089-y 10.1038/s41591-020-01143-2 10.1186/gb-2014-15-2-r29 10.1002/jmv.26213 10.1056/NEJMc2200133 10.1038/s41591-020-0819-2 10.3389/fimmu.2018.00678 10.12688/f1000research.9501.2 10.1016/j.immuni.2021.08.001 10.3389/fimmu.2022.798300 10.1016/j.immuni.2020.04.023 10.3389/fimmu.2017.00019 10.1016/j.chom.2021.05.010 10.4049/jimmunol.168.11.5954 10.1101/2020.06.12.148916 10.1038/s41590-020-0762-x 10.1128/JVI.02670-05 10.1016/j.tube.2012.03.008 10.1093/bioinformatics/btu138 10.1089/aid.2016.0171 10.1371/journal.ppat.1009761 10.1038/nm917 10.1038/s41423-021-00750-4 10.1101/2020.11.15.383323 10.1093/nar/gkt382 10.1016/S0140-6736(21)00575-4 10.1371/journal.pmed.1003656 10.1146/annurev.immunol.18.1.561 10.1002/j.1538-7305.1948.tb01338.x 10.1146/annurev-immunol-031210-101400 10.1101/gr.092759.109 10.1016/j.xcrm.2021.100204 10.3389/fimmu.2013.00095 10.1038/s41586-020-2598-9 10.1038/s41591-022-02078-6 10.1084/jem.164.4.1114 10.1016/j.immuni.2010.12.012 10.1016/j.celrep.2022.110345 10.1182/blood-2003-08-2765 10.1016/j.isci.2020.101212 10.1016/j.isci.2021.103656 10.1016/j.cell.2021.04.048 10.1016/j.immuni.2021.04.006 10.21203/rs.3.rs-51964/v1 10.1182/blood-2006-11-056168 10.1056/NEJMra1204186 10.1016/j.vaccine.2016.09.009 10.1016/S2055-6640(20)30056-X 10.1038/s41564-022-01135-7 10.1038/280147a0 10.1371/journal.pone.0074946 10.1016/j.immuni.2021.04.009 10.1093/bioinformatics/btv359 10.3389/fimmu.2021.708523 10.1097/QAD.0000000000002503 10.1038/nmeth.4380 10.1126/science.abd3871 10.4049/jimmunol.144.2.574 10.1016/j.cell.2020.05.015 10.21105/joss.01686 10.1093/nar/gkz874 10.1126/science.abg8985 10.18637/jss.v067.i08 10.1016/j.immuni.2008.04.018 10.4049/jimmunol.0803548 10.1128/JVI.00249-06 10.3389/fimmu.2017.00376 10.1080/19420862.2021.1922134 10.1186/s13059-019-1874-1 10.1126/science.abf4063 10.1038/s41467-021-24377-1 10.1093/bioinformatics/btw777 10.3389/fimmu.2019.01844 10.1002/eji.201344102 10.1126/sciimmunol.abd2071 10.1101/2021.02.15.431212 10.1038/s41591-020-0995-0 10.1038/ni1515 10.1016/j.cell.2020.02.052 10.1038/s41590-021-01113-x 10.5694/mja2.50963 10.1128/jvi.00128-22 10.1126/sciimmunol.abe4782
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Copyright	Copyright © 2022 Phetsouphanh, Khoo, Jackson, Klemm, Howe, Aggarwal, Akerman, Milogiannakis, Stella, Rouet, Schofield, Faulks, Law, Danwilai, Starr, Munier, Christ, Singh, Croucher, Brilot-Turville, Turville, Phan, Dore, Darley, Cunningham, Matthews, Kelleher and Zaunders. Copyright © 2022 Phetsouphanh, Khoo, Jackson, Klemm, Howe, Aggarwal, Akerman, Milogiannakis, Stella, Rouet, Schofield, Faulks, Law, Danwilai, Starr, Munier, Christ, Singh, Croucher, Brilot-Turville, Turville, Phan, Dore, Darley, Cunningham, Matthews, Kelleher and Zaunders 2022 Phetsouphanh, Khoo, Jackson, Klemm, Howe, Aggarwal, Akerman, Milogiannakis, Stella, Rouet, Schofield, Faulks, Law, Danwilai, Starr, Munier, Christ, Singh, Croucher, Brilot-Turville, Turville, Phan, Dore, Darley, Cunningham, Matthews, Kelleher and Zaunders
Copyright_xml	– notice: Copyright © 2022 Phetsouphanh, Khoo, Jackson, Klemm, Howe, Aggarwal, Akerman, Milogiannakis, Stella, Rouet, Schofield, Faulks, Law, Danwilai, Starr, Munier, Christ, Singh, Croucher, Brilot-Turville, Turville, Phan, Dore, Darley, Cunningham, Matthews, Kelleher and Zaunders. – notice: Copyright © 2022 Phetsouphanh, Khoo, Jackson, Klemm, Howe, Aggarwal, Akerman, Milogiannakis, Stella, Rouet, Schofield, Faulks, Law, Danwilai, Starr, Munier, Christ, Singh, Croucher, Brilot-Turville, Turville, Phan, Dore, Darley, Cunningham, Matthews, Kelleher and Zaunders 2022 Phetsouphanh, Khoo, Jackson, Klemm, Howe, Aggarwal, Akerman, Milogiannakis, Stella, Rouet, Schofield, Faulks, Law, Danwilai, Starr, Munier, Christ, Singh, Croucher, Brilot-Turville, Turville, Phan, Dore, Darley, Cunningham, Matthews, Kelleher and Zaunders
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Keywords	neutralizing antibodies SARS-CoV-2 CD4 T cells CD4 function proliferation
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Vijayakumar Velu, Emory University, United States These authors have contributed equally to this work This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology Reviewed by: Nanda Kishore Routhu, Emory Vaccine Center, School of Medicine, Emory University, United States; Anusmita Sahoo, Emory Vaccine Center, School of Medicine, Emory University, United States
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References	Phetsouphanh (B30) 2022; 23 Hsu (B33) 2012; 92 Hafemeister (B40) 2019; 20 Phetsouphanh (B69) 2013; 8 Dan (B59) 2021; 371 Thevarajan (B75) 2020; 26 Lun (B41) 2016; 5 Juno (B14) 2020; 26 Wickham (B49) 2019; 4 Essalmani (B80) 2022; 96 Li (B85) 2022; 13 McCarthy (B42) 2017; 33 Rouet (B31) 2021; 13 Xu (B68) 2017; 8 Lineburg (B26) 2021; 54 Juno (B74) 2017; 8 Ni (B16) 2020; 52 Hao (B48) 2021; 184 Dan (B7) 2020; 371 Sette (B83) 2008; 28 Darley (B29) 2021; 214 Morita (B70) 2011; 34 Zaunders (B62) 2006; 80 Painter (B8) 2021; 54 Zaunders (B13) 2013; 4 Balachandran (B57) 2022; 38 Nabel (B4) 2013; 368 Mateus (B60) 2020; 370 Gimenez (B25) 2021; 93 Krzywinski (B52) 2009; 19 Low (B21) 2021; 372 Seddiki (B56) 2014; 44 Zaunders (B20) 2009; 183 Zaunders (B34) 2019; 5 Tea (B35) 2021; 18 Bagaev (B54) 2019; 48 Hansen (B1) 2021; 397 Kaufmann (B63) 2007; 8 Mentzer (B87) 2022 Zaunders (B32) 2020; 34 Russell (B81) 1979; 280 Nguyen (B28) 2021; 54 Zaunders (B71) 2004; 103 Stuart (B39) 2019; 177 Shannon (B50) 1948; 27 Ye (B46) 2013; 41 Law (B67) 2022; 25 Jaimes (B78) 2020; 23 Grifoni (B86) 2021; 29 Jung (B19) 2021; 12 Stoeckius (B38) 2017; 14 Vander Heiden (B45) 2014; 30 Massey (B44) 2022; 13 Crotty (B5) 2011; 29 Wolfl (B55) 2007; 110 Schulien (B27) 2021; 27 Hey-Nguyen (B66) 2017; 33 Law (B43) 2014; 15 Anderson (B76) 1990; 144 Hammarlund (B11) 2003; 9 Meckiff (B61) 2020 Xiang (B6) 2021; 12 Grifoni (B15) 2020; 181 Braun (B18) 2020; 587 Aggarwal (B37) 2022; 7 Weiskopf (B17) 2020; 5 Kusnadi (B24) 2021; 6 Schmidt (B22) 2018; 9 Boppana (B64) 2021; 17 Tarke (B65) 2021; 2 Appay (B72) 2002; 168 Khoury (B58) 2021; 27 Phetsouphanh (B73) 2019; 10 Marcon (B51) 2015; 67 Zhang (B77) 2020; 21 Rha (B23) 2021; 18 Altarawneh (B2) 2022; 386 Gupta (B47) 2015; 31 Munier (B10) 2016; 34 Fontanet (B3) 2020; 20 Nolan (B53) 2020 Zaunders (B9) 2006; 80 Scherle (B82) 1986; 164 Doherty (B12) 2000; 18 Hoffmann (B79) 2020; 181 Follenzi (B36) 2002 Sztain (B84) 2021
References_xml	– volume: 20 year: 2020 ident: B3 article-title: COVID-19 herd immunity: Where are we publication-title: Nat Rev Immunol doi: 10.1038/s41577-020-00451-5 – volume: 177 start-page: 1888 year: 2019 ident: B39 article-title: Comprehensive integration of single-cell data publication-title: Cell doi: 10.1016/j.cell.2019.05.031 – volume: 27 year: 2021 ident: B58 article-title: Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection publication-title: Nat Med doi: 10.1038/s41591-021-01377-8 – volume: 13 start-page: 460 year: 2022 ident: B85 article-title: Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 delta variant publication-title: Nat Commun doi: 10.1038/s41467-022-28089-y – volume: 27 start-page: 78 year: 2021 ident: B27 article-title: Characterization of pre-existing and induced SARS-CoV-2-specific CD8(+) T cells publication-title: Nat Med doi: 10.1038/s41591-020-01143-2 – volume: 15 start-page: R29 year: 2014 ident: B43 article-title: Voom: Precision weights unlock linear model analysis tools for RNA-seq read counts publication-title: Genome Biol doi: 10.1186/gb-2014-15-2-r29 – volume: 93 year: 2021 ident: B25 article-title: SARS-CoV-2-reactive interferon-gamma-producing CD8+ T cells in patients hospitalized with coronavirus disease 2019 publication-title: J Med Virol doi: 10.1002/jmv.26213 – volume: 386 year: 2022 ident: B2 article-title: Protection against the omicron variant from previous SARS-CoV-2 infection publication-title: New Engl J Med doi: 10.1056/NEJMc2200133 – volume: 26 year: 2020 ident: B75 article-title: Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19 publication-title: Nat Med doi: 10.1038/s41591-020-0819-2 – volume: 9 year: 2018 ident: B22 article-title: The CD8 T cell response to respiratory virus infections publication-title: Front Immunol doi: 10.3389/fimmu.2018.00678 – volume: 5 start-page: 2122 year: 2016 ident: B41 article-title: A step-by-step workflow for low-level analysis of single-cell RNA-seq data with bioconductor publication-title: F1000Res doi: 10.12688/f1000research.9501.2 – volume: 54 start-page: 2133 year: 2021 ident: B8 article-title: Rapid induction of antigen-specific CD4(+) T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination publication-title: Immunity doi: 10.1016/j.immuni.2021.08.001 – volume: 13 year: 2022 ident: B44 article-title: Haematopoietic stem cell transplantation results in extensive remodelling of the clonal T cell repertoire in multiple sclerosis publication-title: Front Immunol doi: 10.3389/fimmu.2022.798300 – volume: 52 start-page: 971 year: 2020 ident: B16 article-title: Detection of SARS-CoV-2-Specific humoral and cellular immunity in COVID-19 convalescent individuals publication-title: Immunity doi: 10.1016/j.immuni.2020.04.023 – volume: 8 year: 2017 ident: B74 article-title: Cytotoxic CD4 T cells-friend or foe during viral infection publication-title: Front Immunol doi: 10.3389/fimmu.2017.00019 – volume: 29 year: 2021 ident: B86 article-title: SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19 publication-title: Cell Host Microbe doi: 10.1016/j.chom.2021.05.010 – volume: 168 year: 2002 ident: B72 article-title: Characterization of CD4(+) CTLs ex vivo publication-title: J Immunol doi: 10.4049/jimmunol.168.11.5954 – start-page: 3641939 year: 2020 ident: B61 article-title: Single-cell transcriptomic analysis of SARS-CoV-2 reactive CD4 (+) T cells publication-title: SSRN doi: 10.1101/2020.06.12.148916 – volume: 21 year: 2020 ident: B77 article-title: Single-cell landscape of immunological responses in patients with COVID-19 publication-title: Nat Immunol doi: 10.1038/s41590-020-0762-x – volume: 80 year: 2006 ident: B9 article-title: CD127+CCR5+CD38+++ CD4+ Th1 effector cells are an early component of the primary immune response to vaccinia virus and precede development of interleukin-2+ memory CD4+ T cells publication-title: J Virol doi: 10.1128/JVI.02670-05 – volume: 92 year: 2012 ident: B33 article-title: A novel assay detecting recall response to mycobacterium tuberculosis: Comparison with existing assays publication-title: Tuberculosis (Edinb) doi: 10.1016/j.tube.2012.03.008 – volume: 30 year: 2014 ident: B45 article-title: pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires publication-title: Bioinformatics doi: 10.1093/bioinformatics/btu138 – volume: 33 year: 2017 ident: B66 article-title: Quantification of residual germinal center activity and HIV-1 DNA and RNA levels using fine needle biopsies of lymph nodes during antiretroviral therapy publication-title: AIDS Res Hum Retroviruses doi: 10.1089/aid.2016.0171 – volume: 17 year: 2021 ident: B64 article-title: SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence publication-title: PloS Pathog doi: 10.1371/journal.ppat.1009761 – volume-title: Gene therapy protocols year: 2002 ident: B36 – volume: 9 year: 2003 ident: B11 article-title: Duration of antiviral immunity after smallpox vaccination publication-title: Nat Med doi: 10.1038/nm917 – volume: 18 year: 2021 ident: B23 article-title: Activation or exhaustion of CD8(+) T cells in patients with COVID-19 publication-title: Cell Mol Immunol doi: 10.1038/s41423-021-00750-4 – volume: 371 year: 2020 ident: B7 article-title: Immunological memory to SARS-CoV-2 assessed for up to eight months after infection publication-title: bioRxiv doi: 10.1101/2020.11.15.383323 – volume: 41 year: 2013 ident: B46 article-title: IgBLAST: an immunoglobulin variable domain sequence analysis tool publication-title: Nucleic Acids Res doi: 10.1093/nar/gkt382 – volume: 397 year: 2021 ident: B1 article-title: Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study publication-title: Lancet doi: 10.1016/S0140-6736(21)00575-4 – volume: 18 start-page: e1003656 year: 2021 ident: B35 article-title: SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants publication-title: PloS Med doi: 10.1371/journal.pmed.1003656 – volume: 18 year: 2000 ident: B12 article-title: Accessing complexity: the dynamics of virus-specific T cell responses publication-title: Annu Rev Immunol doi: 10.1146/annurev.immunol.18.1.561 – volume: 27 start-page: 379 year: 1948 ident: B50 article-title: A mathematical theory of communication publication-title: Bell System Tech J doi: 10.1002/j.1538-7305.1948.tb01338.x – volume: 29 year: 2011 ident: B5 article-title: Follicular helper CD4 T cells (TFH) publication-title: Annu Rev Immunol doi: 10.1146/annurev-immunol-031210-101400 – volume: 19 year: 2009 ident: B52 article-title: Circos: an information aesthetic for comparative genomics publication-title: Genome Res doi: 10.1101/gr.092759.109 – volume: 2 start-page: 100204 year: 2021 ident: B65 article-title: Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases publication-title: Cell Rep Med doi: 10.1016/j.xcrm.2021.100204 – volume: 4 year: 2013 ident: B13 article-title: Innate and adaptive immunity in long-term non-progression in HIV disease publication-title: Front Immunol doi: 10.3389/fimmu.2013.00095 – volume: 587 year: 2020 ident: B18 article-title: SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19 publication-title: Nature doi: 10.1038/s41586-020-2598-9 – year: 2022 ident: B87 article-title: Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection publication-title: Nat Med doi: 10.1038/s41591-022-02078-6 – volume: 164 year: 1986 ident: B82 article-title: Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for b cell responses to hemagglutinin publication-title: J Exp Med doi: 10.1084/jem.164.4.1114 – volume: 34 year: 2011 ident: B70 article-title: Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion publication-title: Immunity doi: 10.1016/j.immuni.2010.12.012 – volume: 38 start-page: 110345 year: 2022 ident: B57 article-title: Maintenance of broad neutralizing antibodies and memory b cells 1 year post-infection is predicted by SARS-CoV-2-specific CD4+ T cell responses publication-title: Cell Rep doi: 10.1016/j.celrep.2022.110345 – volume: 103 year: 2004 ident: B71 article-title: Identification of circulating antigen-specific CD4+ T lymphocytes with a CCR5+, cytotoxic phenotype in an HIV-1 long-term nonprogressor and in CMV infection publication-title: Blood doi: 10.1182/blood-2003-08-2765 – volume: 23 start-page: 101212 year: 2020 ident: B78 article-title: Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site publication-title: iScience doi: 10.1016/j.isci.2020.101212 – volume: 25 start-page: 103656 year: 2022 ident: B67 article-title: Early expansion of CD38+ICOS+ GC tfh in draining lymph nodes during influenza vaccination immune response publication-title: iScience doi: 10.1016/j.isci.2021.103656 – volume: 184 start-page: 3573 year: 2021 ident: B48 article-title: Integrated analysis of multimodal single-cell data publication-title: Cell doi: 10.1016/j.cell.2021.04.048 – volume: 54 start-page: 1055 year: 2021 ident: B26 article-title: CD8(+) T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses publication-title: Immunity doi: 10.1016/j.immuni.2021.04.006 – year: 2020 ident: B53 article-title: A large-scale database of T-cell receptor beta (TCRβ) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2 publication-title: Res Sq doi: 10.21203/rs.3.rs-51964/v1 – volume: 110 year: 2007 ident: B55 article-title: Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities publication-title: Blood doi: 10.1182/blood-2006-11-056168 – volume: 368 year: 2013 ident: B4 article-title: Designing tomorrow's vaccines publication-title: N Engl J Med doi: 10.1056/NEJMra1204186 – volume: 34 year: 2016 ident: B10 article-title: The primary immune response to vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype publication-title: Vaccine doi: 10.1016/j.vaccine.2016.09.009 – volume: 5 start-page: 73 year: 2019 ident: B34 article-title: Possible clearance of transfusion-acquired nef/LTR-deleted attenuated HIV-1 infection by an elite controller with CCR5 Δ32 heterozygous and HLA-B57 genotype publication-title: J Virus Eradication doi: 10.1016/S2055-6640(20)30056-X – volume: 7 year: 2022 ident: B37 article-title: Platform for isolation and characterization of SARS-CoV-2 variants enables rapid characterisation of omicron in Australia publication-title: Nat Microbiol doi: 10.1038/s41564-022-01135-7 – volume: 280 year: 1979 ident: B81 article-title: T Cells primed by influenza virion internal components can cooperate in the antibody response to haemagglutinin publication-title: Nature doi: 10.1038/280147a0 – volume: 8 year: 2013 ident: B69 article-title: Characterization of transcription factor phenotypes within antigen-specific CD4+ T cells using qualitative multiplex single-cell RT-PCR publication-title: PloS One doi: 10.1371/journal.pone.0074946 – volume: 54 start-page: 1066 year: 2021 ident: B28 article-title: CD8(+) T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity publication-title: Immunity doi: 10.1016/j.immuni.2021.04.009 – volume: 31 year: 2015 ident: B47 article-title: Change-O: a toolkit for analyzing large-scale b cell immunoglobulin repertoire sequencing data publication-title: Bioinformatics doi: 10.1093/bioinformatics/btv359 – volume: 12 year: 2021 ident: B6 article-title: Declining levels of neutralizing antibodies against SARS-CoV-2 in convalescent COVID-19 patients one year post symptom onset publication-title: Front Immunol doi: 10.3389/fimmu.2021.708523 – volume: 34 year: 2020 ident: B32 article-title: Mapping the extent of heterogeneity of human CCR5+ CD4+ T cells in peripheral blood and lymph nodes publication-title: AIDS doi: 10.1097/QAD.0000000000002503 – volume: 14 year: 2017 ident: B38 article-title: Simultaneous epitope and transcriptome measurement in single cells publication-title: Nat Methods doi: 10.1038/nmeth.4380 – volume: 370 year: 2020 ident: B60 article-title: Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans publication-title: Science doi: 10.1126/science.abd3871 – volume: 144 year: 1990 ident: B76 article-title: A monoclonal antibody reactive with a 15-kDa cytoplasmic granule- associated protein defines a subpopulation of CD8+ T lymphocytes publication-title: J Immunol doi: 10.4049/jimmunol.144.2.574 – volume: 181 start-page: 1489 year: 2020 ident: B15 article-title: Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals publication-title: Cell doi: 10.1016/j.cell.2020.05.015 – volume: 4 year: 2019 ident: B49 article-title: Welcome to the tidyverse publication-title: J Open Source Software doi: 10.21105/joss.01686 – volume: 48 year: 2019 ident: B54 article-title: VDJdb in 2019: Database extension, new analysis infrastructure and a T-cell receptor motif compendium publication-title: Nucleic Acids Res doi: 10.1093/nar/gkz874 – volume: 372 year: 2021 ident: B21 article-title: Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2 publication-title: Science doi: 10.1126/science.abg8985 – volume: 67 start-page: 1 year: 2015 ident: B51 article-title: Entropart: An r package to measure and partition diversity publication-title: J Stat Software doi: 10.18637/jss.v067.i08 – volume: 28 year: 2008 ident: B83 article-title: Selective CD4+ T cell help for antibody responses to a large viral pathogen: deterministic linkage of specificities publication-title: Immunity doi: 10.1016/j.immuni.2008.04.018 – volume: 183 year: 2009 ident: B20 article-title: High levels of human antigen-specific CD4+ T cells in peripheral blood revealed by stimulated coexpression of CD25 and CD134 (OX40) publication-title: J Immunol doi: 10.4049/jimmunol.0803548 – volume: 80 year: 2006 ident: B62 article-title: Infection of CD127+ (interleukin-7 receptor+) CD4+ cells and overexpression of CTLA-4 are linked to loss of antigen-specific CD4 T cells during primary human immunodeficiency virus type 1 infection publication-title: J Virol doi: 10.1128/JVI.00249-06 – volume: 8 year: 2017 ident: B68 article-title: HIV-1 and SIV predominantly use CCR5 expressed on a precursor population to establish infection in T follicular helper cells publication-title: Front Immunol doi: 10.3389/fimmu.2017.00376 – volume: 13 start-page: 1922134 year: 2021 ident: B31 article-title: Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies publication-title: MAbs doi: 10.1080/19420862.2021.1922134 – volume: 20 start-page: 296 year: 2019 ident: B40 article-title: Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression publication-title: Genome Biol doi: 10.1186/s13059-019-1874-1 – volume: 371 year: 2021 ident: B59 article-title: Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection publication-title: Science doi: 10.1126/science.abf4063 – volume: 12 start-page: 4043 year: 2021 ident: B19 article-title: SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells publication-title: Nat Commun doi: 10.1038/s41467-021-24377-1 – volume: 33 year: 2017 ident: B42 article-title: Scater: pre-processing, quality control, normalization and visualization of single-cell RNA-seq data in r publication-title: Bioinformatics doi: 10.1093/bioinformatics/btw777 – volume: 10 year: 2019 ident: B73 article-title: Maintenance of functional CD57+ cytolytic CD4+ T cells in HIV+ elite controllers publication-title: Front Immunol doi: 10.3389/fimmu.2019.01844 – volume: 44 year: 2014 ident: B56 article-title: Human antigen-specific CD4(+) CD25(+) CD134(+) CD39(+) T cells are enriched for regulatory T cells and comprise a substantial proportion of recall responses publication-title: Eur J Immunol doi: 10.1002/eji.201344102 – volume: 5 year: 2020 ident: B17 article-title: Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome publication-title: Sci Immunol doi: 10.1126/sciimmunol.abd2071 – year: 2021 ident: B84 article-title: A glycan gate controls opening of the SARS-CoV-2 spike protein publication-title: bioRxiv doi: 10.1101/2021.02.15.431212 – volume: 26 year: 2020 ident: B14 article-title: Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19 publication-title: Nat Med doi: 10.1038/s41591-020-0995-0 – volume: 8 year: 2007 ident: B63 article-title: Upregulation of CTLA-4 by HIV-specific CD4(+) T cells correlates with disease progression and defines a reversible immune dysfunction publication-title: Nat Immunol doi: 10.1038/ni1515 – volume: 181 start-page: 271 year: 2020 ident: B79 article-title: SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor publication-title: Cell doi: 10.1016/j.cell.2020.02.052 – volume: 23 year: 2022 ident: B30 article-title: Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection publication-title: Nat Immunol doi: 10.1038/s41590-021-01113-x – volume: 214 year: 2021 ident: B29 article-title: Persistent symptoms up to four months after community and hospital-managed SARS-CoV-2 infection publication-title: Med J Aust doi: 10.5694/mja2.50963 – volume: 96 year: 2022 ident: B80 article-title: Distinctive roles of furin and TMPRSS2 in SARS-CoV-2 infectivity publication-title: J Virol doi: 10.1128/jvi.00128-22 – volume: 6 year: 2021 ident: B24 article-title: Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8(+) T cells publication-title: Sci Immunol doi: 10.1126/sciimmunol.abe4782
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Snippet	Long-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the... BackgroundLong-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of...
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SubjectTerms	Antibodies, Neutralizing CD4 function CD4 T cells CD4-Positive T-Lymphocytes COVID-19 Epitopes, T-Lymphocyte Humans Immunology neutralizing antibodies proliferation SARS-CoV-2
Title	High titre neutralizing antibodies in response to SARS–CoV–2 infection require RBD–specific CD4 T cells that include proliferative memory cells
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