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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
Nature medicine, 09/2020, Letnik: 26, Številka: 9Journal Article
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts , most targeting the viral 'spike' glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2) . Eliciting neutralizing antibodies that block S-ACE2 interaction , or indirectly prevent membrane fusion , constitute an attractive modality for vaccine-elicited protection . However, although prototypic S-based vaccines show promise in animal models , 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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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