Antibody effector functions are associated with protection from respiratory syncytial virus

被引：43

作者：

Bartsch, Yannic C. ^{[1
,2
]}

Cizmeci, Deniz ^{[1
,2
,3
]}

Kang, Jaewon ^{[1
,2
]}

Zohar, Tomer ^{[1
,2
,3
]}

Periasamy, Sivakumar ^{[4
]}

Mehta, Nickita ^{[1
,2
]}

Tolboom, Jeroen

Van der Fits, Leslie ^{[5
]}

Sadoff, Jerry ^{[5
]}

Comeaux, Christy ^{[5
]}

Callendret, Benoit ^{[5
]}

Bukreyev, Alexander ^{[4
]}

Lauffenburger, Douglas A. ^{[3
]}

Bastian, Arangassery Rosemary ^{[5
]}

Alter, Galit ^{[1
,2
]}

机构：

[1] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA

[2] Harvard, Cambridge, MA 02139 USA

[3] MIT, Dept Biol Engn, Cambridge, MA 02142 USA

[4] Univ Texas Med Branch, Dept Pathol, Galveston Natl Lab, Galveston, TX 77555 USA

[5] Janssen Vaccines & Prevent BV, NL-2333 Leiden, Netherlands

来源：

CELL | 2022年 / 185卷 / 26期

关键词：

FC-GAMMA-RIIB; HIGH-THROUGHPUT; IGG FC; MONOCLONAL-ANTIBODY; VACCINE DEVELOPMENT; BINDING ANTIBODY; RSV INFECTION; IN-VIVO; IMMUNITY; MOUSE;

D O I：

10.1016/j.cell.2022.11.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 im-munity 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-modi-fied monoclonal antibodies able to selectively recruit effector functions demonstrated significant antiviral control in a murine model of RSV.

引用

页码：4873 / +

页数：25

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