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

• Published in: mBio Vol. 12; no. 1
• Main Authors: Guthmiller, Jenna J., Stovicek, Olivia, Wang, Jiaolong, Changrob, Siriruk, Li, Lei, Halfmann, Peter, Zheng, Nai-Ying, Utset, Henry, Stamper, Christopher T., Dugan, Haley L., Miller, William D., Huang, Min, Dai, Ya-Nan, Nelson, Christopher A., Hall, Paige D., Jansen, Maud, Shanmugarajah, Kumaran, Donington, Jessica S., Krammer, Florian, Fremont, Daved H., Joachimiak, Andrzej, Kawaoka, Yoshihiro, Tesic, Vera, Madariaga, Maria Lucia, Wilson, Patrick C.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 19.01.2021; American Society for Microbiology (ASM)
• Subjects: 60 APPLIED LIFE SCIENCES; Adult; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigens, Viral - immunology; B-Lymphocytes - immunology; Coronavirus Nucleocapsid Proteins - immunology; COVID-19 - blood; COVID-19 - immunology; COVID-19 - virology; Cross Reactions; Epitopes - immunology; Female; Host-Microbe Biology; Humans; humoral immunity; Immunity, Humoral - immunology; infection severity; Male; memory B cells; Middle Aged; neutralizing antibodies; Phosphoproteins - immunology; Research Article; SARS-CoV-2; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - immunology; neutralizing antibodies; SARS-CoV-2; humoral immunity; infection severity; memory B cells
• ISSN: 2161-2129; 2150-7511; 2150-7511
• DOI: 10.1128/mBio.02940-20

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. 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.