IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2

Malika Hale; Jason Netland; Yu Chen; Christopher D. Thouvenel; Katherine Nabel Smith; Lucille M. Rich; Elizabeth R. Vanderwall; Marcos C. Miranda; Julie Eggenberger; Linhui Hao; Michael J. Watson; Charles C. Mundorff; Lauren B. Rodda; Neil P. King; Miklos Guttman; Michael Gale; Jonathan Abraham; Jason S. Debley; Marion Pepper; David J. Rawlings

doi:10.1084/jem.20220849

IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2

Malika Hale, Jason Netland, Yu Chen, Christopher D. Thouvenel, Katherine Nabel Smith, Lucille M. Rich, Elizabeth R. Vanderwall, Marcos C. Miranda, Julie Eggenberger, Linhui Hao, Michael J. Watson, Charles C. Mundorff, Lauren B. Rodda, Neil P. King, Miklos Guttman, Michael Gale, Jonathan Abraham, Jason S. Debley, Marion Pepper, David J. Rawlings

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

11 Scopus citations

Abstract

Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera’s neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM⁺ memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen.

Original language	English (US)
Article number	e20220849
Journal	Journal of Experimental Medicine
Volume	219
Issue number	9
DOIs	https://doi.org/10.1084/jem.20220849
State	Published - Sep 5 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 Hale et al.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1084/jem.20220849

Find It

Find It at U of M Libraries

Cite this

Hale, M., Netland, J., Chen, Y., Thouvenel, C. D., Smith, K. N., Rich, L. M., Vanderwall, E. R., Miranda, M. C., Eggenberger, J., Hao, L., Watson, M. J., Mundorff, C. C., Rodda, L. B., King, N. P., Guttman, M., Gale, M., Abraham, J., Debley, J. S., Pepper, M., & Rawlings, D. J. (2022). IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2. Journal of Experimental Medicine, 219(9), Article e20220849. https://doi.org/10.1084/jem.20220849

Hale, M, Netland, J, Chen, Y, Thouvenel, CD, Smith, KN, Rich, LM, Vanderwall, ER, Miranda, MC, Eggenberger, J, Hao, L, Watson, MJ, Mundorff, CC, Rodda, LB, King, NP, Guttman, M, Gale, M, Abraham, J, Debley, JS, Pepper, M & Rawlings, DJ 2022, 'IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2', Journal of Experimental Medicine, vol. 219, no. 9, e20220849. https://doi.org/10.1084/jem.20220849

@article{b807dcc0c03f442e963ffc5a66064705,

title = "IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2",

abstract = "Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera{\textquoteright}s neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM+ memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen.",

author = "Malika Hale and Jason Netland and Yu Chen and Thouvenel, {Christopher D.} and Smith, {Katherine Nabel} and Rich, {Lucille M.} and Vanderwall, {Elizabeth R.} and Miranda, {Marcos C.} and Julie Eggenberger and Linhui Hao and Watson, {Michael J.} and Mundorff, {Charles C.} and Rodda, {Lauren B.} and King, {Neil P.} and Miklos Guttman and Michael Gale and Jonathan Abraham and Debley, {Jason S.} and Marion Pepper and Rawlings, {David J.}",

note = "Publisher Copyright: {\textcopyright} 2022 Hale et al.",

year = "2022",

month = sep,

day = "5",

doi = "10.1084/jem.20220849",

language = "English (US)",

volume = "219",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "9",

}

TY - JOUR

T1 - IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2

AU - Hale, Malika

AU - Netland, Jason

AU - Chen, Yu

AU - Thouvenel, Christopher D.

AU - Smith, Katherine Nabel

AU - Rich, Lucille M.

AU - Vanderwall, Elizabeth R.

AU - Miranda, Marcos C.

AU - Eggenberger, Julie

AU - Hao, Linhui

AU - Watson, Michael J.

AU - Mundorff, Charles C.

AU - Rodda, Lauren B.

AU - King, Neil P.

AU - Guttman, Miklos

AU - Gale, Michael

AU - Abraham, Jonathan

AU - Debley, Jason S.

AU - Pepper, Marion

AU - Rawlings, David J.

PY - 2022/9/5

Y1 - 2022/9/5

N2 - Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera’s neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM+ memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen.

AB - Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera’s neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM+ memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen.

UR - http://www.scopus.com/inward/record.url?scp=85135546828&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85135546828&partnerID=8YFLogxK

U2 - 10.1084/jem.20220849

DO - 10.1084/jem.20220849

M3 - Article

C2 - 35938988

AN - SCOPUS:85135546828

SN - 0022-1007

VL - 219

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 9

M1 - e20220849

ER -

IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2

Abstract

Bibliographical note

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this