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mBio . SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike

tetano

Editor, Senior Moderator
mBio


. 2021 Jan 19;12(1):e02940-20.
doi: 10.1128/mBio.02940-20.
SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike


Jenna J Guthmiller[SUP] #[/SUP][SUP] 1 [/SUP], Olivia Stovicek[SUP] #[/SUP][SUP] 2 [/SUP], Jiaolong Wang[SUP] #[/SUP][SUP] 2 [/SUP], Siriruk Changrob[SUP] 2 [/SUP], Lei Li[SUP] 2 [/SUP], Peter Halfmann[SUP] 3 [/SUP], Nai-Ying Zheng[SUP] 2 [/SUP], Henry Utset[SUP] 2 [/SUP], Christopher T Stamper[SUP] 4 [/SUP], Haley L Dugan[SUP] 4 [/SUP], William D Miller[SUP] 5 [/SUP], Min Huang[SUP] 2 [/SUP], Ya-Nan Dai[SUP] 6 [/SUP], Christopher A Nelson[SUP] 6 [/SUP], Paige D Hall[SUP] 6 [/SUP], Maud Jansen[SUP] 7 [/SUP], Kumaran Shanmugarajah[SUP] 8 [/SUP], Jessica S Donington[SUP] 8 [/SUP], Florian Krammer[SUP] 9 [/SUP], Daved H Fremont[SUP] 6 [/SUP], Andrzej Joachimiak[SUP] 10 11 [/SUP], Yoshihiro Kawaoka[SUP] 3 [/SUP], Vera Tesic[SUP] 12 [/SUP], Maria Lucia Madariaga[SUP] 8 [/SUP], Patrick C Wilson[SUP] 1 4 [/SUP]



Affiliations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.IMPORTANCE With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Subjects who mounted a larger response against the spike also mounted antibody responses against other viral antigens, including the nucleocapsid protein and ORF8. Additionally, this study reveals that subjects with more severe disease mount a larger memory B cell response against the spike. These data suggest that subjects with more severe COVID-19 disease are likely better protected from reinfection with SARS-CoV-2.

Keywords: SARS-CoV-2; humoral immunity; infection severity; memory B cells; neutralizing antibodies.
 
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