Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans
Tom Wilkinson,Li Ckf.,Chui Csc.,Huang Aky.,Huang Aky.,Molly R. Perkins,Julia C. Liebner,Rob Lambkin-Williams,Anthony Gilbert,J. Oxford,Ben Nicholas,Karl J. Staples,Tao Dong,Daniel C. Douek,Andrew J. McMichael,Xiao-Ning Xu +15 more
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TLDR
Inf influenza infection studies in healthy volunteers with no detectable antibodies to the challenge viruses H3N2 or H1N1 are conducted, finding a large increase in influenza-specific T cell responses by day 7, when virus was completely cleared from nasal samples and serum antibodies were still undetectable.Abstract:
Protective immunity against influenza virus infection is mediated by neutralizing antibodies, but the precise role of T cells in human influenza immunity is uncertain. We conducted influenza infection studies in healthy volunteers with no detectable antibodies to the challenge viruses H3N2 or H1N1. We mapped T cell responses to influenza before and during infection. We found a large increase in influenza-specific T cell responses by day 7, when virus was completely cleared from nasal samples and serum antibodies were still undetectable. Preexisting CD4+, but not CD8+, T cells responding to influenza internal proteins were associated with lower virus shedding and less severe illness. These CD4+ cells also responded to pandemic H1N1 (A/CA/07/2009) peptides and showed evidence of cytotoxic activity. These cells are an important statistical correlate of homotypic and heterotypic response and may limit severity of influenza infection by new strains in the absence of specific antibody responses. Our results provide information that may aid the design of future vaccines against emerging influenza strains.read more
Citations
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Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals.
Alba Grifoni,Daniela Weiskopf,Sydney I. Ramirez,Sydney I. Ramirez,Jose Mateus,Jennifer M. Dan,Jennifer M. Dan,Carolyn Rydyznski Moderbacher,Stephen A. Rawlings,Aaron Sutherland,Lakshmanane Premkumar,Ramesh Jadi,Daniel Marrama,Aravinda M. de Silva,April Frazier,Aaron F. Carlin,Jason A. Greenbaum,Bjoern Peters,Bjoern Peters,Florian Krammer,Davey M. Smith,Shane Crotty,Shane Crotty,Alessandro Sette,Alessandro Sette +24 more
TL;DR: Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS.
Journal ArticleDOI
Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19.
Takuya Sekine,André Perez-Potti,Olga Rivera-Ballesteros,Kristoffer Strålin,Jean Baptiste Gorin,Annika Olsson,Sian Llewellyn-Lacey,Habiba Kamal,Gordana Bogdanovic,Sandra Muschiol,David J. Wullimann,Tobias Kammann,Johanna Emgård,Tiphaine Parrot,Elin Folkesson,Olav Rooyackers,Lars Eriksson,Jan-Inge Henter,Anders Sönnerborg,Tobias Allander,Jan Albert,Morten Nielsen,Jonas Klingström,Sara Gredmark-Russ,Niklas K. Björkström,Johan K. Sandberg,David Price,Hans-Gustaf Ljunggren,Soo Aleman,Marcus Buggert +29 more
TL;DR: It is shown that SARS-CoV-2 elicits robust, broad and highly functional memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.
Journal ArticleDOI
Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications
Divij Mathew,Josephine R. Giles,Amy E. Baxter,Derek A. Oldridge,Allison R. Greenplate,Jennifer E. Wu,Cécile Alanio,Leticia Kuri-Cervantes,M. Betina Pampena,Kurt D'Andrea,Sasikanth Manne,Zeyu Chen,Yinghui Jane Huang,John P. Reilly,Ariel R. Weisman,Caroline A. G. Ittner,Oliva Kuthuru,Jeanette Dougherty,Kito Nzingha,Nicholas Han,Justin Kim,Ajinkya Pattekar,Eileen C. Goodwin,Elizabeth M. Anderson,Madison E. Weirick,Sigrid Gouma,Claudia P. Arevalo,Marcus J. Bolton,Fang Chen,Simon F. Lacey,Holly Ramage,Sara Cherry,Scott E. Hensley,Sokratis A. Apostolidis,Alexander C. Huang,Laura A. Vella,Laura A. Vella,Michael R. Betts,Nuala J. Meyer,E. John Wherry +39 more
TL;DR: High-dimensional flow cytometry of hospitalized COVID-19 patients found three prominent and distinct immunotypes that are related to disease severity and clinical parameters, and a compendium of immune cell information and roadmaps for potential therapeutic interventions is provided.
Journal ArticleDOI
Adaptive immunity to SARS-CoV-2 and COVID-19.
TL;DR: In this article, a picture has begun to emerge that reveals that CD4+ T cells, CD8+ Tcells, and neutralizing antibodies all contribute to control SARS-CoV-2 in both non-hospitalized and hospitalized cases of COVID-19.
Journal ArticleDOI
Broad and strong memory CD4 + and CD8 + T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19.
Yanchun Peng,Alexander J. Mentzer,G Liu,G Liu,X Yao,Z Yin,D Dong,D Dong,Wanwisa Dejnirattisai,T Rostron,P Supasa,C Liu,Cesar Lopez-Camacho,J Slon-Campos,Yuguang Zhao,David I. Stuart,Guido C. Paesen,Jonathan M. Grimes,Alfred A. Antson,Oliver W. Bayfield,Hawkins Dedp.,Ker D-S.,B Wang,Lance Turtle,Krishanthi Subramaniam,Paul Thomson,P Zhang,Christina Dold,Jeremy Ratcliff,Peter Simmonds,T I de Silva,Paul Sopp,Dannielle Wellington,U S Rajapaksa,Chen Y-L.,Mariolina Salio,Giorgio Napolitani,Wayne Paes,Persephone Borrow,Benedikt M. Kessler,J W Fry,N F Schwabe,Malcolm G Semple,Malcolm G Semple,J K Baillie,Shona C Moore,Openshaw Pjm.,M A Ansari,Susanna Dunachie,Eleanor Barnes,John Frater,G Kerr,Philip J. R. Goulder,T Lockett,R Levin,Y Zhang,Y Zhang,R Jing,Ho L-P.,Richard J. Cornall,Christopher P. Conlon,Paul Klenerman,Gavin R. Screaton,Juthathip Mongkolsapaya,Andrew J. McMichael,Julian C. Knight,Graham S. Ogg,Tao Dong +67 more
TL;DR: The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.
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