Infectious bursal disease virus suppresses humoral immunity via blocking antibody affinity maturation in chickens

Blockade of antibody affinity maturation causes vaccination failure, yet whether pathogens exploit this process for immunosuppression remains poorly understood. Infectious bursal disease virus (IBDV) causes immunosuppression in chickens, but its underlying mechanism remains unclear. We show that the anti-IBDV VP2 affinity constant (Ka) remained unchanged between primary and secondary responses, indicating antibody affinity maturation failure. In contrast, anti-NDV F protein antibodies exhibited a >4-fold Ka increase upon secondary response, but this increase was abolished by IBDV coinfection. Consistently, anti-NDV HI titers were reduced in NDV and IBDV-coinfected chickens. IBDV infection decreased splenic IgM⁺ B cells and upregulated IL2, IFNG, and activation-induced cytidine deaminase (AID) expression. We identified VP5 and double-stranded RNA (dsRNA as key viral components inducing IFNG and IL2, which skews the immune response toward cellular immunity. These findings identify the blockade of antibody affinity maturation as a key mechanism of IBDV-induced immunosuppression, offering a mechanistic explanation for vaccination failure and viral immune evasion.