TY - JOUR
T1 - SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike
AU - Guthmiller, Jenna J.
AU - Stovicek, Olivia
AU - Wang, Jiaolong
AU - Changrob, Siriruk
AU - Li, Lei
AU - Halfmann, Peter
AU - Zheng, Nai Ying
AU - Utset, Henry
AU - Stamper, Christopher T.
AU - Dugan, Haley L.
AU - Miller, William D.
AU - Huang, Min
AU - Dai, Ya Nan
AU - Nelson, Christopher A.
AU - Hall, Paige D.
AU - Jansen, Maud
AU - Shanmugarajah, Kumaran
AU - Donington, Jessica S.
AU - Krammer, Florian
AU - Fremont, Daved H.
AU - Joachimiak, Andrzej
AU - Kawaoka, Yoshihiro
AU - Tesic, Vera
AU - Madariaga, Maria Lucia
AU - Wilson, Patrick C.
N1 - Funding Information:
This project was funded in part by the National Institute of Allergy and Infectious Diseases; National Institutes of Health grant numbers U19AI082724 (P.C.W.), U19AI109946 (P.C.W.), and U19AI057266 (P.C.W.). This work was also partially supported by the National Institute of Allergy and Infectious Diseases Collaborative Influenza Vaccine Innovation Centers (CIVIC; 75N93019C00051, F.K. and P.C.W.) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS) HHSN272201400008C (F.K.) and by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272201700060C (A.J., D.H.F.). This work was also supported by the National Heart, Lung, Blood Institute award T32HL007605-35 (J.J.G.).
Publisher Copyright:
© 2021 Guthmiller et al.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - Humoral immunity
KW - Infection severity
KW - Memory B cells
KW - Neutralizing antibodies
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85100004121&partnerID=8YFLogxK
U2 - 10.1128/mBio.02940-20
DO - 10.1128/mBio.02940-20
M3 - Article
C2 - 33468695
AN - SCOPUS:85100004121
SN - 2161-2129
VL - 12
SP - 1
EP - 13
JO - mBio
JF - mBio
IS - 1
M1 - e02940-20
ER -