tetano
Editor, Senior Moderator
Nat Med
. 2020 Jul 13.
doi: 10.1038/s41591-020-0995-0. Online ahead of print.
Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
Jennifer A Juno[SUP] 1 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Wen Shi Lee[SUP] 1 [/SUP], Arnold Reynaldi[SUP] 2 [/SUP], Hannah G Kelly[SUP] 1 3 [/SUP], Kathleen Wragg[SUP] 1 [/SUP], Robyn Esterbauer[SUP] 1 3 [/SUP], Helen E Kent[SUP] 1 4 [/SUP], C Jane Batten[SUP] 1 [/SUP], Francesca L Mordant[SUP] 1 [/SUP], Nicholas A Gherardin[SUP] 1 5 [/SUP], Phillip Pymm[SUP] 6 7 [/SUP], Melanie H Dietrich[SUP] 6 7 [/SUP], Nichollas E Scott[SUP] 1 [/SUP], Wai-Hong Tham[SUP] 6 [/SUP], Dale I Godfrey[SUP] 1 5 [/SUP], Kanta Subbarao[SUP] 1 8 [/SUP], Miles P Davenport[SUP] 2 [/SUP], Stephen J Kent[SUP] 9 10 11 [/SUP], Adam K Wheatley[SUP] 12 13 [/SUP]
Affiliations
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts[SUP]1-3[/SUP], most targeting the viral 'spike' glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)[SUP]4-6[/SUP]. Eliciting neutralizing antibodies that block S-ACE2 interaction[SUP]7-9[/SUP], or indirectly prevent membrane fusion[SUP]10[/SUP], constitute an attractive modality for vaccine-elicited protection[SUP]11[/SUP]. However, although prototypic S-based vaccines show promise in animal models[SUP]12-14[/SUP], 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.
. 2020 Jul 13.
doi: 10.1038/s41591-020-0995-0. Online ahead of print.
Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
Jennifer A Juno[SUP] 1 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Wen Shi Lee[SUP] 1 [/SUP], Arnold Reynaldi[SUP] 2 [/SUP], Hannah G Kelly[SUP] 1 3 [/SUP], Kathleen Wragg[SUP] 1 [/SUP], Robyn Esterbauer[SUP] 1 3 [/SUP], Helen E Kent[SUP] 1 4 [/SUP], C Jane Batten[SUP] 1 [/SUP], Francesca L Mordant[SUP] 1 [/SUP], Nicholas A Gherardin[SUP] 1 5 [/SUP], Phillip Pymm[SUP] 6 7 [/SUP], Melanie H Dietrich[SUP] 6 7 [/SUP], Nichollas E Scott[SUP] 1 [/SUP], Wai-Hong Tham[SUP] 6 [/SUP], Dale I Godfrey[SUP] 1 5 [/SUP], Kanta Subbarao[SUP] 1 8 [/SUP], Miles P Davenport[SUP] 2 [/SUP], Stephen J Kent[SUP] 9 10 11 [/SUP], Adam K Wheatley[SUP] 12 13 [/SUP]
Affiliations
- PMID: 32661393
- DOI: 10.1038/s41591-020-0995-0
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts[SUP]1-3[/SUP], most targeting the viral 'spike' glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)[SUP]4-6[/SUP]. Eliciting neutralizing antibodies that block S-ACE2 interaction[SUP]7-9[/SUP], or indirectly prevent membrane fusion[SUP]10[/SUP], constitute an attractive modality for vaccine-elicited protection[SUP]11[/SUP]. However, although prototypic S-based vaccines show promise in animal models[SUP]12-14[/SUP], 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.