Bovine Adenovirus 3-Based Viral Vectors for Veterinary Vaccine Development: Progress, Limitations, and Future Directions

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Bovine adenovirus (BAdV)-based vectors, particularly those derived from bovine adenovirus 3 (BAdV-3), are emerging non-human adenoviral platforms for veterinary vaccine development. Adenoviral vectors are attractive for vaccination because they mediate efficient transgene expression, remain largely episomal, and induce robust innate and adaptive immune responses. However, widely used human adenoviral vectors, especially human adenovirus 5 (HAdV-5), may be compromised by pre-existing anti-vector immunity, supporting the development of rare human serotypes and non-human adenoviral alternatives. BAdV-3 is the best-characterized BAdV for recombinant vector engineering and has been used to express heterologous antigens from bovine herpesvirus-1, bovine respiratory syncytial virus, influenza virus, and Mycobacterium tuberculosis. Available evidence indicates that BAdV-based vectors can induce humoral, cellular, and mucosal immune responses and support intranasal antigen delivery. Protective efficacy has been demonstrated in selected experimental models, including mice and ferrets for influenza and tuberculosis vaccine candidates, whereas cattle challenge evidence remains more limited and is primarily represented by BHV-1 gD-expressing BAdV-3 vectors. These features make BAdV vectors relevant to bovine respiratory disease control, livestock vaccination, and One Health-oriented vaccine preparedness. Nevertheless, the platform remains at an early developmental stage. Key gaps include limited target-species efficacy data, pre-existing BAdV immunity in cattle, vector shedding, recombination risk, genetic stability, producer cell optimization, manufacturing scalability, and regulatory feasibility.