Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
Open accessAbstract
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 fusion 10, constitute an attractive modality for vaccine-elicited protection 11. 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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SARS-CoV-2 spike-specific circulating TFH cell responses correlate with generation of neutralizing antibodies in convalescent individuals, particularly when the cells have a CCR6- phenotype.
“SARS-CoV-2 spike-specific circulating TFH cell responses correlate with the generation of neutralizing antibodies in convalescent individuals, particularly when these cells have a CCR6– phenotype32.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [32]
Healthy adults commonly show CD4+ T cell memory against hCoVs.
“several studies indicate the presence of widespread CD4+ T cell memory to hCoVs among healthy adults32,79–81.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [32]
Spike is a good target for CD4+ T cell, Tfh cell, and CD8+ T cell responses in people infected with SARS-CoV-2.
“the findings that Spike is a good target for CD4+ T cell responses, Tfh cell responses, and CD8+ T cell responses in SARS-CoV-2-infected people”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Juno et al., 2020
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- Authors
- Juno, J. A., Tan, H.-X., Lee, W. S., Reynaldi, A., Kelly, H. G., Wragg, K., Esterbauer, R., Kent, H. E., Batten, C. J., Mordant, F. L., Gherardin, N. A., Pymm, P., Dietrich, M. H., Scott, N. E., Tham, W.-H., Godfrey, D. I., Subbarao, K., Davenport, M. P., Kent, S. J., & Wheatley, A. K.
- Affiliations
- The University of Melbourne (AU)
- UNSW Sydney (AU)
- Australian Research Council (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Corresponding author
- Kent, Stephen J.
- Wheatley, Adam K.
- ORCID
- Venue
- Nature Medicine
- Published
- 2020-07-13
- Volume
- 26
- Issue
- 9
- Pages
- 1428-1434
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3041502662
- Cited by
- 437
- References
- 55
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 36 · 2023: 55 · 2022: 115 · 2021: 140 · 2020: 60
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- Monash University Research Portal (Monash University) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion)
- Funders
- Department of Health | National Health and Medical Research Council (GNT1162760, 1123673, APP1149990)
- The Jack Ma Foundation
- The Jack Ma Foundation A2 Milk Company
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, COVID-19 pandemic, spike protein, humoral immunity, neutralizing antibodies, memory B cells, vaccine biomarkers, receptor binding domain, recovered patients
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, Animals, Antibodies, Viral, Epitopes, Antigens, Viral, Chlorocebus aethiops, T-Lymphocytes, Helper-Inducer, Humans, Immunity, Cellular, Peptidyl-Dipeptidase A, Pneumonia, Viral, Vero Cells, Coronavirus Infections, Antibodies, Neutralizing, Pandemics, Spike Glycoprotein, Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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