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

• Published in: Nature medicine Vol. 26; no. 9; pp. 1428 - 1434
• Main Authors: Juno, Jennifer A., Tan, Hyon-Xhi, Lee, Wen Shi, Reynaldi, Arnold, Kelly, Hannah G., Wragg, Kathleen, Esterbauer, Robyn, Kent, Helen E., Batten, C. Jane, Mordant, Francesca L., Gherardin, Nicholas A., Pymm, Phillip, Dietrich, Melanie H., Scott, Nichollas E., Tham, Wai-Hong, Godfrey, Dale I., Subbarao, Kanta, Davenport, Miles P., Kent, Stephen J., Wheatley, Adam K.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2020; Nature Publishing Group
• Subjects: 631/250/1619/40; 631/250/1619/554/1898/1270; 631/250/2152/2153/1291; 631/250/255/2514; ACE2; Angiotensin; Angiotensin-Converting Enzyme 2; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - pharmacology; Antibodies, Viral - immunology; Antibodies, Viral - pharmacology; Antigens, Viral - immunology; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; CCR6 protein; Cell differentiation; Chlorocebus aethiops; Circulation; Coronaviridae; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronavirus Infections - virology; Coronaviruses; COVID-19; COVID-19 vaccines; CXCR3 protein; Epitopes; Epitopes - immunology; Glycoproteins; Health aspects; Humans; Humoral immunity; Immune response; Immunity; Immunity, Cellular - immunology; Immunogenicity; Immunological memory; Infectious Diseases; Letter; Lymphocytes; Lymphocytes B; Lymphocytes T; Memory cells; Metabolic Diseases; Molecular Medicine; Neurosciences; Neutralizing; Pandemics; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - immunology; Phenotypes; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; Receptors; Recognition; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - antagonists & inhibitors; Spike Glycoprotein, Coronavirus - immunology; Spikes; T cells; T-Lymphocytes, Helper-Inducer - immunology; Vaccine development; Vaccines; Vero Cells - immunology; Viral antibodies; Viral diseases; Virions; Viruses; Australia
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-020-0995-0

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts 1 , 2 – 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 , 5 – 6 . Eliciting neutralizing antibodies that block S–ACE2 interaction 7 , 8 – 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 , 13 – 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. In a cohort of recovered patients with COVID-19, virus spike-specific antibodies were consistently elicited, but neutralizing activity was highly variable and inversely correlated with the proportion of CCR6 + CXCR3 − spike-specific circulating follicular helper T cells.