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Antibody effector functions are associated with protection from respiratory syncytial virus.
Bartsch, Yannic C; Cizmeci, Deniz; Kang, Jaewon; Zohar, Tomer; Periasamy, Sivakumar; Mehta, Nickita; Tolboom, Jeroen; Van der Fits, Leslie; Sadoff, Jerry; Comeaux, Christy; Callendret, Benoit; Bukreyev, Alexander; Lauffenburger, Douglas A; Bastian, Arangassery Rosemary; Alter, Galit.
Affiliation
  • Bartsch YC; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Cizmeci D; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Kang J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Zohar T; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Periasamy S; Department of Pathology, Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Mehta N; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Tolboom J; Janssen Vaccines & Prevention BV, 2333 Leiden, the Netherlands.
  • Van der Fits L; Janssen Vaccines & Prevention BV, 2333 Leiden, the Netherlands.
  • Sadoff J; Janssen Vaccines & Prevention BV, 2333 Leiden, the Netherlands.
  • Comeaux C; Janssen Vaccines & Prevention BV, 2333 Leiden, the Netherlands.
  • Callendret B; Janssen Vaccines & Prevention BV, 2333 Leiden, the Netherlands.
  • Bukreyev A; Department of Pathology, Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Lauffenburger DA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Bastian AR; Janssen Vaccines & Prevention BV, 2333 Leiden, the Netherlands. Electronic address: ARosema1@its.jnj.com.
  • Alter G; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: galter@mgh.harvard.edu.
Cell ; 185(26): 4873-4886.e10, 2022 12 22.
Article in En | MEDLINE | ID: mdl-36513064
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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Full text: 1 Database: MEDLINE Main subject: Respiratory Syncytial Virus, Human / Respiratory Syncytial Virus Infections Type of study: Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Year: 2022 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Respiratory Syncytial Virus, Human / Respiratory Syncytial Virus Infections Type of study: Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Year: 2022 Type: Article