SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike

Jenna J. Guthmiller, Olivia Stovicek, Jiaolong Wang, Siriruk Changrob, Lei Li, Peter Halfmann, Nai Ying Zheng, Henry Utset, Christopher T. Stamper, Haley L. Dugan, William D. Miller, Min Huang, Ya Nan Dai, Christopher A. Nelson, Paige D. Hall, Maud Jansen, Kumaran Shanmugarajah, Jessica S. Donington, Florian Krammer, Daved H. FremontAndrzej Joachimiak, Yoshihiro Kawaoka, Vera Tesic, Maria Lucia Madariaga, Patrick C. Wilson

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is cur-rently 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.

Original languageEnglish
Article numbere02940-20
Pages (from-to)1-13
Number of pages13
JournalmBio
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2021

Keywords

  • Humoral immunity
  • Infection severity
  • Memory B cells
  • Neutralizing antibodies
  • SARS-CoV-2

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