A recombinant human adenovirus type 5 vectored vaccine co-expression of VP1 and VP2 of chicken anemia virus elicits robust protective immune responses

Chicken anemia virus (CAV) causes significant economic losses in the poultry industry worldwide. As current vaccines do not confer complete protection, the development of a highly effective and safe vaccine is of paramount importance. Control strategies relying on live attenuated vaccines carry a risk of reversion to virulence, while conventional inactivated or subunit vaccines preferentially induce a Th2-biased humoral immune response. There often fail to elicit the critical Th1-mediated cellular immunity required to clear infected cells. This immunological imbalance underscores the need for a vaccine that activates both arms of the adaptive immune system. Here, we constructed a recombinant adenovirus, rAd5-CAV-VP1-VP2, which co-expresses two CAV antigens, leveraging the intrinsic ability of adenoviral vectors to induce a balanced Th1/Th2 response and utilizing the chaperone-like function of VP2 to ensure the correct conformational folding of VP1. Vaccination trials demonstrated that the rAd5-CAV-VP1-VP2 is safe and highly immunogenic, characterized by significantly upregulated levels of interferon-gamma (IFN-γ) and interleukin-4 (IL-4), and accompanied by high-titer VP1-specific antibodies. Crucially, upon challenge with a virulent CAV strain, the vaccinated chicks exhibited complete protection against mortality (100 %, 25/25), a significant alleviation of clinical symptoms, and prevention of the thymic atrophy and bone marrow failure. In conclusion, rAd5-CAV-VP1-VP2 elicits a robust and comprehensive immune response that effectively protects against CAV-induced clinical and pathological damage, presenting a promising, strategy for the control of chicken infectious anemia (CIA).