Antibody effector functions are associated with protection from respiratory syncytial virus

Yannic C. Bartsch; Deniz Cizmeci; Jaewon Kang; Tomer Zohar; Sivakumar Periasamy; Nickita Mehta; Jeroen Tolboom; Leslie Van der Fits; Jerry Sadoff; Christy Comeaux; Benoit Callendret; Alexander Bukreyev; Douglas A. Lauffenburger; Arangassery Rosemary Bastian; Galit Alter

doi:10.1016/j.cell.2022.11.012

Antibody effector functions are associated with protection from respiratory syncytial virus

Yannic C. Bartsch, Deniz Cizmeci, Jaewon Kang, Tomer Zohar, Sivakumar Periasamy, Nickita Mehta, Jeroen Tolboom, Leslie Van der Fits, Jerry Sadoff, Christy Comeaux, Benoit Callendret, Alexander Bukreyev, Douglas A. Lauffenburger, Arangassery Rosemary Bastian, Galit Alter

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

26 Scopus citations

Abstract

Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory tract infection and death in young infants and the elderly. With no effective prophylactic treatment available, current vaccine candidates aim to elicit neutralizing antibodies. However, binding and neutralization have poorly predicted protection in the past, and accumulating data across epidemiologic cohorts and animal models collectively point to a role for additional antibody Fc-effector functions. To begin to define the humoral correlates of immunity against RSV, here we profiled an adenovirus 26 RSV-preF vaccine-induced humoral immune response in a group of healthy adults that were ultimately challenged with RSV. Protection from infection was linked to opsonophagocytic functions, driven by IgA and differentially glycosylated RSV-specific IgG profiles, marking a functional humoral immune signature of protection against RSV. Furthermore, Fc-modified monoclonal antibodies able to selectively recruit effector functions demonstrated significant antiviral control in a murine model of RSV.

Original language	English (US)
Pages (from-to)	4873-4886.e10
Journal	Cell
Volume	185
Issue number	26
DOIs	https://doi.org/10.1016/j.cell.2022.11.012
State	Published - Dec 22 2022
Externally published	Yes

Keywords

Ad26
Fc effector functions
Fc glycosylation
IgA
RSV
antibodies
human challenge study
mAbs
vaccination

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2022.11.012

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Bartsch, Y. C., Cizmeci, D., Kang, J., Zohar, T., Periasamy, S., Mehta, N., Tolboom, J., Van der Fits, L., Sadoff, J., Comeaux, C., Callendret, B., Bukreyev, A., Lauffenburger, D. A., Bastian, A. R., & Alter, G. (2022). Antibody effector functions are associated with protection from respiratory syncytial virus. Cell, 185(26), 4873-4886.e10. https://doi.org/10.1016/j.cell.2022.11.012

Bartsch, YC, Cizmeci, D, Kang, J, Zohar, T, Periasamy, S, Mehta, N, Tolboom, J, Van der Fits, L, Sadoff, J, Comeaux, C, Callendret, B, Bukreyev, A, Lauffenburger, DA, Bastian, AR & Alter, G 2022, 'Antibody effector functions are associated with protection from respiratory syncytial virus', Cell, vol. 185, no. 26, pp. 4873-4886.e10. https://doi.org/10.1016/j.cell.2022.11.012

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abstract = "Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory tract infection and death in young infants and the elderly. With no effective prophylactic treatment available, current vaccine candidates aim to elicit neutralizing antibodies. However, binding and neutralization have poorly predicted protection in the past, and accumulating data across epidemiologic cohorts and animal models collectively point to a role for additional antibody Fc-effector functions. To begin to define the humoral correlates of immunity against RSV, here we profiled an adenovirus 26 RSV-preF vaccine-induced humoral immune response in a group of healthy adults that were ultimately challenged with RSV. Protection from infection was linked to opsonophagocytic functions, driven by IgA and differentially glycosylated RSV-specific IgG profiles, marking a functional humoral immune signature of protection against RSV. Furthermore, Fc-modified monoclonal antibodies able to selectively recruit effector functions demonstrated significant antiviral control in a murine model of RSV.",

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author = "Bartsch, {Yannic C.} and Deniz Cizmeci and Jaewon Kang and Tomer Zohar and Sivakumar Periasamy and Nickita Mehta and Jeroen Tolboom and {Van der Fits}, Leslie and Jerry Sadoff and Christy Comeaux and Benoit Callendret and Alexander Bukreyev and Lauffenburger, {Douglas A.} and Bastian, {Arangassery Rosemary} and Galit Alter",

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doi = "10.1016/j.cell.2022.11.012",

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AU - Periasamy, Sivakumar

AU - Mehta, Nickita

AU - Tolboom, Jeroen

AU - Van der Fits, Leslie

AU - Sadoff, Jerry

AU - Comeaux, Christy

AU - Callendret, Benoit

AU - Bukreyev, Alexander

AU - Lauffenburger, Douglas A.

AU - Bastian, Arangassery Rosemary

AU - Alter, Galit

PY - 2022/12/22

Y1 - 2022/12/22

N2 - Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory tract infection and death in young infants and the elderly. With no effective prophylactic treatment available, current vaccine candidates aim to elicit neutralizing antibodies. However, binding and neutralization have poorly predicted protection in the past, and accumulating data across epidemiologic cohorts and animal models collectively point to a role for additional antibody Fc-effector functions. To begin to define the humoral correlates of immunity against RSV, here we profiled an adenovirus 26 RSV-preF vaccine-induced humoral immune response in a group of healthy adults that were ultimately challenged with RSV. Protection from infection was linked to opsonophagocytic functions, driven by IgA and differentially glycosylated RSV-specific IgG profiles, marking a functional humoral immune signature of protection against RSV. Furthermore, Fc-modified monoclonal antibodies able to selectively recruit effector functions demonstrated significant antiviral control in a murine model of RSV.

AB - Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory tract infection and death in young infants and the elderly. With no effective prophylactic treatment available, current vaccine candidates aim to elicit neutralizing antibodies. However, binding and neutralization have poorly predicted protection in the past, and accumulating data across epidemiologic cohorts and animal models collectively point to a role for additional antibody Fc-effector functions. To begin to define the humoral correlates of immunity against RSV, here we profiled an adenovirus 26 RSV-preF vaccine-induced humoral immune response in a group of healthy adults that were ultimately challenged with RSV. Protection from infection was linked to opsonophagocytic functions, driven by IgA and differentially glycosylated RSV-specific IgG profiles, marking a functional humoral immune signature of protection against RSV. Furthermore, Fc-modified monoclonal antibodies able to selectively recruit effector functions demonstrated significant antiviral control in a murine model of RSV.

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Antibody effector functions are associated with protection from respiratory syncytial virus

Abstract

Keywords

ASJC Scopus subject areas

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