Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

Mehul S. Suthar; Matthew G. Zimmerman; Robert C. Kauffman; Grace Mantus; Susanne L. Linderman; William H. Hudson; Abigail Vanderheiden; Lindsay Nyhoff; Carl W. Davis; Oluwaseyi Adekunle; Maurizio Affer; Melanie Sherman; Stacian Reynolds; Hans P. Verkerke; David N. Alter; Jeannette Guarner; Janetta Bryksin; Michael C. Horwath; Connie M. Arthur; Natia Saakadze; Geoffrey H. Smith; Srilatha Edupuganti; Erin M. Scherer; Kieffer Hellmeister; Andrew Cheng; Juliet A. Morales; Andrew S. Neish; Sean R. Stowell; Filipp Frank; Eric Ortlund; Evan J. Anderson; Vineet D. Menachery; Nadine Rouphael; Aneesh K. Mehta; David S. Stephens; Rafi Ahmed; John D. Roback; Jens Wrammert

doi:10.1016/j.xcrm.2020.100040

Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

Mehul S. Suthar, Matthew G. Zimmerman, Robert C. Kauffman, Grace Mantus, Susanne L. Linderman, William H. Hudson, Abigail Vanderheiden, Lindsay Nyhoff, Carl W. Davis, Oluwaseyi Adekunle, Maurizio Affer, Melanie Sherman, Stacian Reynolds, Hans P. Verkerke, David N. Alter, Jeannette Guarner, Janetta Bryksin, Michael C. Horwath, Connie M. Arthur, Natia SaakadzeGeoffrey H. Smith, Srilatha Edupuganti, Erin M. Scherer, Kieffer Hellmeister, Andrew Cheng, Juliet A. Morales, Andrew S. Neish, Sean R. Stowell, Filipp Frank, Eric Ortlund, Evan J. Anderson, Vineet D. Menachery, Nadine Rouphael, Aneesh K. Mehta, David S. Stephens, Rafi Ahmed, John D. Roback, Jens Wrammert

Microbiology And Immunology

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

392 Scopus citations

Abstract

SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.

Original language	English (US)
Article number	100040
Journal	Cell Reports Medicine
Volume	1
Issue number	3
DOIs	https://doi.org/10.1016/j.xcrm.2020.100040
State	Published - Jun 23 2020

Keywords

COVID-19
SARS-CoV-2
coronavirus
humoral immune response
neutralizing antibody
protective immunity
receptor-binding protein
serology test
spike protein

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2020.100040

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Suthar, M. S., Zimmerman, M. G., Kauffman, R. C., Mantus, G., Linderman, S. L., Hudson, W. H., Vanderheiden, A., Nyhoff, L., Davis, C. W., Adekunle, O., Affer, M., Sherman, M., Reynolds, S., Verkerke, H. P., Alter, D. N., Guarner, J., Bryksin, J., Horwath, M. C., Arthur, C. M., ... Wrammert, J. (2020). Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients. Cell Reports Medicine, 1(3), Article 100040. https://doi.org/10.1016/j.xcrm.2020.100040

Suthar, MS, Zimmerman, MG, Kauffman, RC, Mantus, G, Linderman, SL, Hudson, WH, Vanderheiden, A, Nyhoff, L, Davis, CW, Adekunle, O, Affer, M, Sherman, M, Reynolds, S, Verkerke, HP, Alter, DN, Guarner, J, Bryksin, J, Horwath, MC, Arthur, CM, Saakadze, N, Smith, GH, Edupuganti, S, Scherer, EM, Hellmeister, K, Cheng, A, Morales, JA, Neish, AS, Stowell, SR, Frank, F, Ortlund, E, Anderson, EJ, Menachery, VD, Rouphael, N, Mehta, AK, Stephens, DS, Ahmed, R, Roback, JD & Wrammert, J 2020, 'Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients', Cell Reports Medicine, vol. 1, no. 3, 100040. https://doi.org/10.1016/j.xcrm.2020.100040

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title = "Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients",

abstract = "SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.",

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author = "Suthar, {Mehul S.} and Zimmerman, {Matthew G.} and Kauffman, {Robert C.} and Grace Mantus and Linderman, {Susanne L.} and Hudson, {William H.} and Abigail Vanderheiden and Lindsay Nyhoff and Davis, {Carl W.} and Oluwaseyi Adekunle and Maurizio Affer and Melanie Sherman and Stacian Reynolds and Verkerke, {Hans P.} and Alter, {David N.} and Jeannette Guarner and Janetta Bryksin and Horwath, {Michael C.} and Arthur, {Connie M.} and Natia Saakadze and Smith, {Geoffrey H.} and Srilatha Edupuganti and Scherer, {Erin M.} and Kieffer Hellmeister and Andrew Cheng and Morales, {Juliet A.} and Neish, {Andrew S.} and Stowell, {Sean R.} and Filipp Frank and Eric Ortlund and Anderson, {Evan J.} and Menachery, {Vineet D.} and Nadine Rouphael and Mehta, {Aneesh K.} and Stephens, {David S.} and Rafi Ahmed and Roback, {John D.} and Jens Wrammert",

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doi = "10.1016/j.xcrm.2020.100040",

language = "English (US)",

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AU - Suthar, Mehul S.

AU - Zimmerman, Matthew G.

AU - Kauffman, Robert C.

AU - Mantus, Grace

AU - Linderman, Susanne L.

AU - Hudson, William H.

AU - Vanderheiden, Abigail

AU - Nyhoff, Lindsay

AU - Davis, Carl W.

AU - Adekunle, Oluwaseyi

AU - Affer, Maurizio

AU - Sherman, Melanie

AU - Reynolds, Stacian

AU - Verkerke, Hans P.

AU - Alter, David N.

AU - Guarner, Jeannette

AU - Bryksin, Janetta

AU - Horwath, Michael C.

AU - Arthur, Connie M.

AU - Saakadze, Natia

AU - Smith, Geoffrey H.

AU - Edupuganti, Srilatha

AU - Scherer, Erin M.

AU - Hellmeister, Kieffer

AU - Cheng, Andrew

AU - Morales, Juliet A.

AU - Neish, Andrew S.

AU - Stowell, Sean R.

AU - Frank, Filipp

AU - Ortlund, Eric

AU - Anderson, Evan J.

AU - Menachery, Vineet D.

AU - Rouphael, Nadine

AU - Mehta, Aneesh K.

AU - Stephens, David S.

AU - Ahmed, Rafi

AU - Roback, John D.

AU - Wrammert, Jens

PY - 2020/6/23

Y1 - 2020/6/23

N2 - SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.

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KW - humoral immune response

KW - neutralizing antibody

KW - protective immunity

KW - receptor-binding protein

KW - serology test

KW - spike protein

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SN - 2666-3791

VL - 1

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M1 - 100040

ER -

Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

Abstract

Keywords

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