Chicken infectious Anemia virus impairs vaccination-induced antibody responses by suppressing CD40L expression.

Chicken Infectious Anemia Virus (CIAV), a small non-enveloped single-stranded DNA virus, primarily induces immunosuppression via thymus T cell precursor apoptosis and T cell depletion. Recent studies have suggested that CIAV-mediated immunosuppression involves unconventional mechanisms beyond thymic apoptosis. However, the molecular underpinnings remain poorly defined. Here, we show that CIAV significantly suppresses vaccine-induced humoral antibody response in chickens by inhibiting splenic T/B lymphocyte activation/function and downregulating multiple immune-related pathways. Notably, we identify the CD40L/CD40 co-stimulatory ligand-receptor pair as a key target for CIAV-mediated humoral immunity subversion. Critically, recombinant CD40L enhances the efficacy of NDV LaSota and inactivated CIAV vaccines as a molecular adjuvant via improving antibody production. Collectively, our findings uncover a novel CIAV immunosuppressive mechanism and highlight CD40L as a promising molecular adjuvant for optimizing next-generation CIAV vaccines.