Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity

Saborni Chakraborty; Joseph C. Gonzalez; Benjamin L. Sievers; Vamsee Mallajosyula; Srijoni Chakraborty; Megha Dubey; Usama Ashraf; Bowie Yik Ling Cheng; Nimish Kathale; Kim Quyen Thi Tran; Courtney Scallan; Aanika Sinnott; Arianna Cassidy; Steven T. Chen; Terri Gelbart; Fei Gao; Yarden Golan; Xuhuai Ji; Seunghee Kim-Schulze; Mary Prahl; Stephanie L. Gaw; Sacha Gnjatic; Thomas U. Marron; Miriam Merad; Prabhu S. Arunachalam; Scott D. Boyd; Mark M. Davis; Marisa Holubar; Chaitan Khosla; Holden T. Maecker; Yvonne Maldonado; Elizabeth D. Mellins; Kari C. Nadeau; Bali Pulendran; Upinder Singh; Aruna Subramanian; Paul J. Utz; Robert Sherwood; Sheng Zhang; Prasanna Jagannathan; Gene S. Tan; Taia T. Wang

doi:10.1126/scitranslmed.abm7853

Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity

Saborni Chakraborty, Joseph C. Gonzalez, Benjamin L. Sievers, Vamsee Mallajosyula, Srijoni Chakraborty, Megha Dubey, Usama Ashraf, Bowie Yik Ling Cheng, Nimish Kathale, Kim Quyen Thi Tran, Courtney Scallan, Aanika Sinnott, Arianna Cassidy, Steven T. Chen, Terri Gelbart, Fei Gao, Yarden Golan, Xuhuai Ji, Seunghee Kim-Schulze, Mary PrahlStephanie L. Gaw, Sacha Gnjatic, Thomas U. Marron, Miriam Merad, Prabhu S. Arunachalam, Scott D. Boyd, Mark M. Davis, Marisa Holubar, Chaitan Khosla, Holden T. Maecker, Yvonne Maldonado, Elizabeth D. Mellins, Kari C. Nadeau, Bali Pulendran, Upinder Singh, Aruna Subramanian, Paul J. Utz, Robert Sherwood, Sheng Zhang, Prasanna Jagannathan, Gene S. Tan, Taia T. Wang

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

29 Scopus citations

Abstract

A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.

Original language	English
Article number	abm7853
Journal	Science Translational Medicine
Volume	14
Issue number	635
DOIs	https://doi.org/10.1126/scitranslmed.abm7853
State	Published - 9 Mar 2022

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Chakraborty, S., Gonzalez, J. C., Sievers, B. L., Mallajosyula, V., Chakraborty, S., Dubey, M., Ashraf, U., Cheng, B. Y. L., Kathale, N., Tran, K. Q. T., Scallan, C., Sinnott, A., Cassidy, A., Chen, S. T., Gelbart, T., Gao, F., Golan, Y., Ji, X., Kim-Schulze, S., ... Wang, T. T. (2022). Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity. Science Translational Medicine, 14(635), [abm7853]. https://doi.org/10.1126/scitranslmed.abm7853

@article{ed3fd5acff884e568a2370ba8f148b86,

title = "Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity",

abstract = "A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.",

author = "Saborni Chakraborty and Gonzalez, {Joseph C.} and Sievers, {Benjamin L.} and Vamsee Mallajosyula and Srijoni Chakraborty and Megha Dubey and Usama Ashraf and Cheng, {Bowie Yik Ling} and Nimish Kathale and Tran, {Kim Quyen Thi} and Courtney Scallan and Aanika Sinnott and Arianna Cassidy and Chen, {Steven T.} and Terri Gelbart and Fei Gao and Yarden Golan and Xuhuai Ji and Seunghee Kim-Schulze and Mary Prahl and Gaw, {Stephanie L.} and Sacha Gnjatic and Marron, {Thomas U.} and Miriam Merad and Arunachalam, {Prabhu S.} and Boyd, {Scott D.} and Davis, {Mark M.} and Marisa Holubar and Chaitan Khosla and Maecker, {Holden T.} and Yvonne Maldonado and Mellins, {Elizabeth D.} and Nadeau, {Kari C.} and Bali Pulendran and Upinder Singh and Aruna Subramanian and Utz, {Paul J.} and Robert Sherwood and Sheng Zhang and Prasanna Jagannathan and Tan, {Gene S.} and Wang, {Taia T.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors.",

year = "2022",

month = mar,

day = "9",

doi = "10.1126/scitranslmed.abm7853",

language = "English",

volume = "14",

journal = "Science Translational Medicine",

issn = "1946-6234",

publisher = "American Association for the Advancement of Science",

number = "635",

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Chakraborty, S, Gonzalez, JC, Sievers, BL, Mallajosyula, V, Chakraborty, S, Dubey, M, Ashraf, U, Cheng, BYL, Kathale, N, Tran, KQT, Scallan, C, Sinnott, A, Cassidy, A, Chen, ST, Gelbart, T, Gao, F, Golan, Y, Ji, X, Kim-Schulze, S, Prahl, M, Gaw, SL, Gnjatic, S , Marron, TU, Merad, M, Arunachalam, PS, Boyd, SD, Davis, MM, Holubar, M, Khosla, C, Maecker, HT, Maldonado, Y, Mellins, ED, Nadeau, KC, Pulendran, B, Singh, U, Subramanian, A, Utz, PJ, Sherwood, R, Zhang, S, Jagannathan, P, Tan, GS & Wang, TT 2022, 'Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity', Science Translational Medicine, vol. 14, no. 635, abm7853. https://doi.org/10.1126/scitranslmed.abm7853

TY - JOUR

T1 - Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity

AU - Chakraborty, Saborni

AU - Gonzalez, Joseph C.

AU - Sievers, Benjamin L.

AU - Mallajosyula, Vamsee

AU - Chakraborty, Srijoni

AU - Dubey, Megha

AU - Ashraf, Usama

AU - Cheng, Bowie Yik Ling

AU - Kathale, Nimish

AU - Tran, Kim Quyen Thi

AU - Scallan, Courtney

AU - Sinnott, Aanika

AU - Cassidy, Arianna

AU - Chen, Steven T.

AU - Gelbart, Terri

AU - Gao, Fei

AU - Golan, Yarden

AU - Ji, Xuhuai

AU - Kim-Schulze, Seunghee

AU - Prahl, Mary

AU - Gaw, Stephanie L.

AU - Gnjatic, Sacha

AU - Marron, Thomas U.

AU - Merad, Miriam

AU - Arunachalam, Prabhu S.

AU - Boyd, Scott D.

AU - Davis, Mark M.

AU - Holubar, Marisa

AU - Khosla, Chaitan

AU - Maecker, Holden T.

AU - Maldonado, Yvonne

AU - Mellins, Elizabeth D.

AU - Nadeau, Kari C.

AU - Pulendran, Bali

AU - Singh, Upinder

AU - Subramanian, Aruna

AU - Utz, Paul J.

AU - Sherwood, Robert

AU - Zhang, Sheng

AU - Jagannathan, Prasanna

AU - Tan, Gene S.

AU - Wang, Taia T.

PY - 2022/3/9

Y1 - 2022/3/9

N2 - A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.

AB - A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.

UR - http://www.scopus.com/inward/record.url?scp=85126152402&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.abm7853

DO - 10.1126/scitranslmed.abm7853

M3 - Article

C2 - 35040666

AN - SCOPUS:85126152402

VL - 14

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 635

M1 - abm7853

ER -

Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity

Abstract

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