Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
- Juno, JA; Tan, HX; Lee, WS; Reynaldi, A; Kelly, HG; Wragg, K; Esterbauer, R; Kent, HE; Batten, CJ; Mordant, FL; Gherardin, NA; Pymm, P; Dietrich, MH; Scott, NE; Tham, WH; Godfrey, DI; Subbarao, K; Davenport, MP; Kent, SJ; Wheatley, AK;
- Journal Title
- Nature Medicine
- Publication Type
- Journal epub ahead of print
- 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.
- WEHI Research Division(s)
- Infectious Diseases And Immune Defence
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-07-21 10:52:55Last Modified: 2020-07-21 11:26:21