Host-targeted oral avian vaccine virus demonstrates broad antiviral activity and safety in patients.

The absence of an immediately deployable, broad-spectrum antiviral remains a critical vulnerability in global pandemic preparedness. Host-directed agents that activate innate immunity offer a pathogen-agnostic strategy, yet no such therapy is currently stockpiled or authorized for emergency use. Infectious Bursal Disease Virus (IBDV)-a non-replicating avian dsRNA vaccine virus with a 60-year safety record in poultry-induces robust interferon responses in mammals and has been administered orally in marmosets and more than 50 human patients with hepatitis A, B, C, SARS-CoV-2, and herpes zoster infections. These observations include a randomized phase II trial in 84 acute HBV/HCV patients. Although the evidence base is limited, the consistency of clinical responses and absence of serious safety signals justify renewed scientific examination. This review synthesizes the mechanistic rationale, comparative advantages over synthetic Pattern Recognition Receptor (PRR) agonists, clinical observations, One Health implications, and regulatory precedents relevant to evaluating IBDV as a temporary, compassionate-use antiviral during pandemics while the reverse-engineered human candidate (IBDV-R903/78) progresses through formal development. The goal is not to endorse clinical deployment, but to initiate a rigorous, multidisciplinary debate on whether an established veterinary dsRNA vaccine virus could serve as an off-the-shelf host-directed live viral adjuvant therapy in future public health emergencies.