Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19

doi:10.1038/s41591-020-0995-0

. 2020 Sep;26(9):1428-1434.

doi: 10.1038/s41591-020-0995-0. Epub 2020 Jul 13.

Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19

Jennifer A Juno^#¹, Hyon-Xhi Tan^#¹, Wen Shi Lee¹, Arnold Reynaldi², Hannah G Kelly^{1

3}, Kathleen Wragg¹, Robyn Esterbauer^{1

3}, Helen E Kent^{1

4}, C Jane Batten¹, Francesca L Mordant¹, Nicholas A Gherardin^{1

5}, Phillip Pymm^{6

7}, Melanie H Dietrich^{6

7}, Nichollas E Scott¹, Wai-Hong Tham⁶, Dale I Godfrey^{1

5}, Kanta Subbarao^{1

8}, Miles P Davenport², Stephen J Kent^#^{9

10

11}, Adam K Wheatley^#^{12

13}

Affiliations

¹ Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
² Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia.
³ Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia.
⁴ Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia.
⁵ Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria, Australia.
⁶ Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
⁷ Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
⁸ WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁹ Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. skent@unimelb.edu.au.
¹⁰ Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia. skent@unimelb.edu.au.
¹¹ Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia. skent@unimelb.edu.au.
¹² Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. awheatley@unimelb.edu.au.
¹³ Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia. awheatley@unimelb.edu.au.

^# Contributed equally.

PMID: 32661393
DOI: 10.1038/s41591-020-0995-0

Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19

Jennifer A Juno et al. Nat Med. 2020 Sep.

. 2020 Sep;26(9):1428-1434.

doi: 10.1038/s41591-020-0995-0. Epub 2020 Jul 13.

Authors

Affiliations

¹ Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
² Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia.
³ Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia.
⁴ Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia.
⁵ Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria, Australia.
⁶ Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
⁷ Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
⁸ WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁹ Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. skent@unimelb.edu.au.
¹⁰ Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia. skent@unimelb.edu.au.
¹¹ Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia. skent@unimelb.edu.au.
¹² Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. awheatley@unimelb.edu.au.
¹³ Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia. awheatley@unimelb.edu.au.

^# Contributed equally.

PMID: 32661393
DOI: 10.1038/s41591-020-0995-0

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts^1-3, 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 interaction^7-9, or indirectly prevent membrane fusion¹⁰, constitute an attractive modality for vaccine-elicited protection¹¹. However, although prototypic S-based vaccines show promise in animal models^12-14, 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.

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References

1. Amanat, F. & Krammer, F. SARS-CoV-2 vaccines: status report. Immunity 52, 583–589 (2020). - PubMed - PMC - DOI
1. Thanh, Le,T. et al. The COVID-19 vaccine development landscape. Nat. Rev. Drug Discov. 19, 305–306 (2020). - DOI
1. Lurie, N., Saville, M., Hatchett, R. & Halton, J. Developing Covid-19 vaccines at pandemic speed. N. Engl. J. Med. 382, 1969–1973 (2020). - PubMed - DOI
1. Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280 (2020). - PubMed - PMC - DOI
1. Yan, R. et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448 (2020). - PubMed - PMC - DOI

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[1] Amanat, F. & Krammer, F. SARS-CoV-2 vaccines: status report. Immunity 52, 583–589 (2020). - PubMed - PMC - DOI

[2] Amanat, F. & Krammer, F. SARS-CoV-2 vaccines: status report. Immunity 52, 583–589 (2020). - PubMed - PMC - DOI

[3] Thanh, Le,T. et al. The COVID-19 vaccine development landscape. Nat. Rev. Drug Discov. 19, 305–306 (2020). - DOI

[4] Thanh, Le,T. et al. The COVID-19 vaccine development landscape. Nat. Rev. Drug Discov. 19, 305–306 (2020). - DOI

[5] Lurie, N., Saville, M., Hatchett, R. & Halton, J. Developing Covid-19 vaccines at pandemic speed. N. Engl. J. Med. 382, 1969–1973 (2020). - PubMed - DOI

[6] Lurie, N., Saville, M., Hatchett, R. & Halton, J. Developing Covid-19 vaccines at pandemic speed. N. Engl. J. Med. 382, 1969–1973 (2020). - PubMed - DOI

[7] Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280 (2020). - PubMed - PMC - DOI

[8] Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280 (2020). - PubMed - PMC - DOI

[9] Yan, R. et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448 (2020). - PubMed - PMC - DOI

[10] Yan, R. et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448 (2020). - PubMed - PMC - DOI

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Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19

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Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19

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