Isotyping and quantitation of the humoral immune response to SARS-CoV-2

Krystal A. Goyins; Jieh Juen Yu; Sara B. Papp; Rachel Beddard; Ashlesh K. Murthy; James P. Chambers; Bernard P. Arulanandam

doi:10.1177/15353702221084966

Isotyping and quantitation of the humoral immune response to SARS-CoV-2

Krystal A. Goyins, Jieh Juen Yu, Sara B. Papp, Rachel Beddard, Ashlesh K. Murthy, James P. Chambers, Bernard P. Arulanandam

Department of Microbiology, Immunology & Molecular Genetics

Research output: Contribution to journal › Article › peer-review

Abstract

Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.

Original language	English (US)
Pages (from-to)	1055-1060
Number of pages	6
Journal	Experimental Biology and Medicine
Volume	247
Issue number	12
DOIs	https://doi.org/10.1177/15353702221084966
State	Published - Jun 2022

Keywords

COVID-19
SARS-CoV-2
antibody
neutralization
plasma
variant

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1177/15353702221084966

Cite this

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title = "Isotyping and quantitation of the humoral immune response to SARS-CoV-2",

abstract = "Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.",

keywords = "COVID-19, SARS-CoV-2, antibody, neutralization, plasma, variant",

author = "Goyins, {Krystal A.} and Yu, {Jieh Juen} and Papp, {Sara B.} and Rachel Beddard and Murthy, {Ashlesh K.} and Chambers, {James P.} and Arulanandam, {Bernard P.}",

note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by The Jane and Roland Blumberg Endowment fund to BPA. Publisher Copyright: {\textcopyright} 2022 by the Society for Experimental Biology and Medicine.",

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language = "English (US)",

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AU - Goyins, Krystal A.

AU - Yu, Jieh Juen

AU - Papp, Sara B.

AU - Beddard, Rachel

AU - Murthy, Ashlesh K.

AU - Chambers, James P.

AU - Arulanandam, Bernard P.

N1 - Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by The Jane and Roland Blumberg Endowment fund to BPA. Publisher Copyright: © 2022 by the Society for Experimental Biology and Medicine.

PY - 2022/6

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N2 - Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.

AB - Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.

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Isotyping and quantitation of the humoral immune response to SARS-CoV-2

Abstract

Keywords

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