Identification of novel T-cell epitopes on viral protein VP4 of Infectious Bursal Disease Virus (IBDV) that play critical roles in eliciting cellular immune response

Infectious bursal disease virus (IBDV) is a highly infectious RNA virus that causes severe damage to the bursa of Fabricius (BF), resulting in immunosuppression. Currently, IBDV vaccines mainly rely on the induction of neutralizing antibodies against VP2 for protection, and the role of cellular immunity against IBDV infection is unclear. Here, we show that IBDV VP4, a serine protease of the virion, is responsible for inducing specific T cell immunity against IBDV infection. Furthermore, we identified three specific T cell epitope peptides on VP4, among which, two epitopes (4/10 and 4/12) could be recognized by CD8+T cells, and the other one (4/27) by both CD4+T cells and CD8+T cells. Importantly, infection of SPF chickens with rFAdV-4-ON1-VP4, which is generated with the backbone of an avirulent fowl adenovirus strain (FAdV-4-ON1) without causing any clinical symptoms in chickens, induced IBDV-specific cellular immunity, providing effective protection for chickens against IBDV infection. This study demonstrates for the first time that the specific cellular immunity induced by IBDV VP4 specific-T cell epitopes plays a protective role in host response against IBDV infection, providing a new insight into the development of novel vaccines for the control of viral diseases.