Agonistic 4-1BB antibody fails to reduce disease burden during acute respiratory syncytial virus (RSV) infection

- The anti-RSV activity of an agonistic 4-1BB antibody delivered at the time of viral infection was tested in mice.
- Neither intra-peritoneal nor intranasal administration of antibody improved disease outcomes.
- Agonistic 4-1BB antibody reduced RSV specific CD8 T cells in the lung and was associated with increased morbidity in mice.
- We suggest caution with in vivo use of agonistic 4-1BB antibody in the setting of acute viral infections.

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.