LPS/TLR4-activated M1-polarized macrophage-derived exosomes enhance IBV vaccine efficacy in chickens

Abstract

Infectious bronchitis virus (IBV) causes significant global economic losses in the poultry industry despite extensive vaccination programs. Current vaccines often fail to elicit sufficient mucosal and cellular immunity, which are critical for protection against the virus. Although commercial adjuvants have been employed to enhance vaccine efficacy, many exhibit limitations in eliciting comprehensive immune responses. In this study, we comprehensively evaluated HD11 M1 -exo as a novel adjuvant for IBV vaccines across in vitro , in ovo , and in vivo models for the first time. Our results demonstrate that HD11 M1 -exo enhances macrophage function via lipopolysaccharide (LPS)/TLR4 signaling, upregulates key cytokines and immune markers in embryonic tissues, and significantly boosts cellular, humoral, and mucosal immunity when co-administered with live-attenuated IBV vaccines, outperforming commercial adjuvants. Importantly, this adjuvant strategy significantly enhanced protective efficacy in challenged chickens. This study provides a foundation for developing exosome-based adjuvants that could advance poultry vaccination strategies against IBV and other avian respiratory pathogens.