title: Agonistic 4-1BB antibody fails to reduce disease burden during acute respiratory syncytial virus (RSV) infection.
abstract: Respiratory Syncytial Virus (RSV) remains a leading cause of infant morbidity and mortality worldwide. Despite this, there are limited therapeutic options. CD8 T cells have an integral role in controlling viral infections; strategies to enhance these responses may be clinically relevant. The T cell costimulatory receptor, 4-1BB, is known to play a role in expansion of antiviral CD8 T cells. In this study, we examined the effect of agonistic 4-1BB antibody at the time of RSV infection in mice. We show that this antibody did not improve outcomes in the setting of RSV infection but rather, led to increased weight loss and a reduction in RSV specific CD8 T cells in the lung. This work suggests caution in the use of agonistic 4-1BB antibody in the setting of viral infections.
authors.affiliation: Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Physiology and Experimental Medicine, SickKids, Toronto, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Norris
authors.affiliation: Physiology and Experimental Medicine, SickKids, Toronto, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Duan
authors.affiliation: Physiology and Experimental Medicine, SickKids, Toronto, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Cen
authors.affiliation: Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Physiology and Experimental Medicine, SickKids, Toronto, Canada. Electronic address: theo.moraes@sickkids.ca.
authors.forename: T J
authors.initials: TJ
authors.lastname: Moraes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061025:Costimulatory and Inhibitory T-Cell Receptors; D018984:Epitopes, T-Lymphocyte; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: Agonistic 4-1BB antibody; CD8 T cells; Costimulation; Respiratory syncytial virus (RSV)