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

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.

• Authors: Jennifer A Juno, Hyon-Xhi Tan, Wen Shi Lee, Arnold Reynaldi, Hannah G Kelly, Kathleen Wragg, Robyn Esterbauer, Helen E Kent, C Jane Batten, Francesca L Mordant, Nicholas A Gherardin, Phillip Pymm, Melanie H Dietrich, Nichollas E Scott, Wai-Hong Tham, Dale I Godfrey, Kanta Subbarao, Miles P Davenport, Stephen J Kent, Adam K Wheatley
• Journal: Nature medicine (Nat Med) Vol. 26 Issue 9 Pg. 1428-1434 (09 2020) ISSN: 1546-170X [Electronic] United States
• PMID: 32661393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Antigens, Viral
• Epitopes
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2
• Peptidyl-Dipeptidase A
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2
• Animals
• Antibodies, Neutralizing (immunology, pharmacology)
• Antibodies, Viral (immunology, pharmacology)
• Antigens, Viral (immunology)
• COVID-19
• Chlorocebus aethiops
• Coronavirus Infections (immunology, pathology, virology)
• Epitopes (immunology)
• Humans
• Immunity, Cellular (immunology)
• Pandemics
• Peptidyl-Dipeptidase A (genetics, immunology)
• Pneumonia, Viral (immunology, pathology, virology)
• Spike Glycoprotein, Coronavirus (antagonists & inhibitors, immunology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Vero Cells (immunology)