Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19.
Jennifer A Juno,Hyon-Xhi Tan,Wen Shi Lee,Arnold Reynaldi,Hannah G. Kelly,Hannah G. Kelly,Kathleen M. Wragg,Robyn Esterbauer,Robyn Esterbauer,Helen E Kent,Helen E Kent,C. Jane Batten,Francesca L Mordant,Nicholas A Gherardin,Nicholas A Gherardin,Phillip Pymm,Phillip Pymm,Melanie H. Dietrich,Melanie H. Dietrich,Nichollas E. Scott,Wai-Hong Tham,Dale I. Godfrey,Dale I. Godfrey,Kanta Subbarao,Miles P. Davenport,Stephen J. Kent,Stephen J. Kent,Stephen J. Kent,Adam K. Wheatley,Adam K. Wheatley +29 more
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TLDR
It is found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and positively associated with plasma neutralizing activity, suggesting that vaccines might require strategies to selectively target the most potent neutralizing epitopes.Abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1-3, most targeting the viral 'spike' glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)4-6. Eliciting neutralizing antibodies that block S-ACE2 interaction7-9, or indirectly prevent membrane fusion10, constitute an attractive modality for vaccine-elicited protection11. However, although prototypic S-based vaccines show promise in animal models12-14, the immunogenic properties of S in humans are poorly resolved. In this study, we characterized humoral and circulating follicular helper T cell (cTFH) immunity against spike in recovered patients with coronavirus disease 2019 (COVID-19). We found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and positively associated with plasma neutralizing activity. Comparatively low frequencies of B cells or cTFH specific for the receptor binding domain of S were elicited. Notably, the phenotype of S-specific cTFH differentiated subjects with potent neutralizing responses, providing a potential biomarker of potency for S-based vaccines entering the clinic. Overall, although patients who recovered from COVID-19 displayed multiple hallmarks of effective immune recognition of S, the wide spectrum of neutralizing activity observed suggests that vaccines might require strategies to selectively target the most potent neutralizing epitopes.read more
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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.
David S. Khoury,Deborah Cromer,Arnold Reynaldi,Timothy E. Schlub,Timothy E. Schlub,Adam K. Wheatley,Jennifer A Juno,Kanta Subbarao,Stephen J. Kent,Stephen J. Kent,Stephen J. Kent,James A. Triccas,Miles P. Davenport +12 more
TL;DR: It is shown that neutralization level is highly predictive of immune protection, and an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic is provided.
Journal ArticleDOI
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.
Jennifer M. Dan,Jennifer M. Dan,Jose Mateus,Yu Kato,Kathryn M. Hastie,Esther Dawen Yu,Caterina E. Faliti,Alba Grifoni,Sydney I. Ramirez,Sydney I. Ramirez,Sonya Haupt,April Frazier,Catherine Nakao,Vamseedhar Rayaprolu,Stephen A. Rawlings,Bjoern Peters,Bjoern Peters,Florian Krammer,Viviana Simon,Erica Ollmann Saphire,Erica Ollmann Saphire,Davey M. Smith,Daniela Weiskopf,Alessandro Sette,Alessandro Sette,Shane Crotty,Shane Crotty +26 more
TL;DR: This article analyzed multiple compartments of circulating immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months after infection.
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
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity.
Carolyn Rydyznski Moderbacher,Sydney I. Ramirez,Sydney I. Ramirez,Jennifer M. Dan,Jennifer M. Dan,Alba Grifoni,Kathryn M. Hastie,Daniela Weiskopf,Simon Bélanger,Robert K. Abbott,Christina K. Kim,Jinyong Choi,Yu Kato,Eleanor G. Crotty,Cheryl Kim,Stephen A. Rawlings,Jose Mateus,Longping V. Tse,April Frazier,Ralph S. Baric,Bjoern Peters,Jason A. Greenbaum,Erica Ollmann Saphire,Erica Ollmann Saphire,Davey M. Smith,Alessandro Sette,Alessandro Sette,Shane Crotty,Shane Crotty +28 more
TL;DR: A combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects suggested roles for both CD4 plus T cells in protective immunity in COVID-19.
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.
References
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Journal ArticleDOI
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Journal ArticleDOI
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
Daniel Wrapp,Nianshuang Wang,Kizzmekia S. Corbett,Jory A. Goldsmith,Ching-Lin Hsieh,Olubukola M. Abiona,Barney S. Graham,Jason S. McLellan +7 more
TL;DR: The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.
Journal ArticleDOI
Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
Jun Lan,Jiwan Ge,Jinfang Yu,Sisi Shan,Huan Zhou,Shilong Fan,Qi Zhang,Xuanling Shi,Qisheng Wang,Linqi Zhang,Xinquan Wang +10 more
TL;DR: High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.
Journal ArticleDOI
Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2.
TL;DR: Cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein of SARS-CoV-2 are presented, providing important insights into the molecular basis for coronavirus recognition and infection.
Journal ArticleDOI
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.
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