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

[tetano]

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



Affiliations

• PMID: 33468695
• DOI: 10.1128/mBio.02940-20

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.