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. 2022 Dec 22;185(26):4873-4886.e10.
doi: 10.1016/j.cell.2022.11.012. Epub 2022 Dec 12.

Antibody effector functions are associated with protection from respiratory syncytial virus

Yannic C Bartsch  1 , Deniz Cizmeci  2 , Jaewon Kang  1 , Tomer Zohar  2 , Sivakumar Periasamy  3 , Nickita Mehta  1 , Jeroen Tolboom  4 , Leslie Van der Fits  4 , Jerry Sadoff  4 , Christy Comeaux  4 , Benoit Callendret  4 , Alexander Bukreyev  3 , Douglas A Lauffenburger  5 , Arangassery Rosemary Bastian  6 , Galit Alter  7
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Free article

Antibody effector functions are associated with protection from respiratory syncytial virus

Yannic C Bartsch et al. Cell. .
Free article

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.

Keywords: Ad26; Fc effector functions; Fc glycosylation; IgA; RSV; antibodies; human challenge study; mAbs; vaccination.

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Conflict of interest statement

Declaration of interests G.A. is a founder of Seromyx Systems and an equity holder in Leyden Labs. G.A. is on a leave of absence and is currently employed by Moderna Inc. J.T., J.S., L.v.d.F., C.C., B.C., and A.R.B. are employed by Janssen Pharmaceuticals, a Johnson & Johnson company, and may be Johnson & Johnson stockholders.

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