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. Fremont; Andrzej Joachimiak; Yoshihiro Kawaoka; Vera Tesic; Maria Lucia Madariaga; Patrick C. Wilson

doi:10.1128/mBio.02940-20

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 journal › Article › peer-review

61 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 language	English
Article number	e02940-20
Pages (from-to)	1-13
Number of pages	13
Journal	mBio
Volume	12
Issue number	1
DOIs	https://doi.org/10.1128/mBio.02940-20
State	Published - 1 Jan 2021

Keywords

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

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10.1128/mBio.02940-20

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Guthmiller, J. J., Stovicek, O., Wang, J., Changrob, S., Li, L., Halfmann, P., Zheng, N. Y., Utset, H., Stamper, C. T., Dugan, H. L., Miller, W. D., Huang, M., Dai, Y. N., Nelson, C. A., Hall, P. D., Jansen, M., Shanmugarajah, K., Donington, J. S., Krammer, F., ... Wilson, P. C. (2021). SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike. mBio, 12(1), 1-13. Article e02940-20. https://doi.org/10.1128/mBio.02940-20

@article{93638c052e18481d8131db18344889eb,

title = "SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike",

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.",

keywords = "Humoral immunity, Infection severity, Memory B cells, Neutralizing antibodies, SARS-CoV-2",

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

note = "Publisher Copyright: {\textcopyright} 2021 Guthmiller et al.",

year = "2021",

month = jan,

day = "1",

doi = "10.1128/mBio.02940-20",

language = "English",

volume = "12",

pages = "1--13",

journal = "mBio",

issn = "2161-2129",

publisher = "American Society for Microbiology",

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Guthmiller, JJ, Stovicek, O, Wang, J, Changrob, S, Li, L, Halfmann, P, Zheng, NY, Utset, H, Stamper, CT, Dugan, HL, Miller, WD, Huang, M, Dai, YN, Nelson, CA, Hall, PD, Jansen, M, Shanmugarajah, K, Donington, JS, Krammer, F, Fremont, DH, Joachimiak, A, Kawaoka, Y, Tesic, V, Madariaga, ML & Wilson, PC 2021, 'SARS-CoV-2 infection severity is linked to superior humoral immunity against the spike', mBio, vol. 12, no. 1, e02940-20, pp. 1-13. https://doi.org/10.1128/mBio.02940-20

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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.

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

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DO - 10.1128/mBio.02940-20

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AN - SCOPUS:85100004121

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JO - mBio

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M1 - e02940-20

ER -

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

Abstract

Keywords

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