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Heterologous DNA-Adenovirus Prime-Boost Strategy Expressing Bluetongue Virus VP2 and VP7 Proteins Protects Against
Pablo Nogales-Altozano1, Laro Gómez-Marcos1, Ana Belén Carlón1
1Centro de Investigación en Sanidad Animal, Instituto de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (CISA-INIA-CSIC), Valdeolmos, 28130 Madrid, Spain.
Background/Objectives:
Bluetongue virus (BTV) is an emerging arbovirus causing significant economic losses in the ruminant industry. Current vaccines offer limited cross-protection against heterologous serotypes and do not enable differentiation between infected and vaccinated animals (DIVA). Subunit-based vaccines provide a potential DIVA-compatible solution. This study aimed to develop a vaccination protocol expressing BTV structural proteins VP7 or VP2 using antibiotic-resistance-free DNA plasmids and replication-defective adenovirus vectors.
Methods:
We evaluated homologous DNA prime-boost and heterologous DNA prime-adenovirus boost strategies in a murine model, assessing adaptive immune responses and protection against virulent BTV challenge.
Results:
The heterologous DNA-adenovirus prime-boost strategy expressing both antigens conferred full protection, preventing viremia, while homologous DNA-DNA prime-boost provided only partial protection. Both VP7 and VP2 elicited cellular and humoral immune responses, but the heterologous strategy significantly enhanced anti-BTV IgG, neutralizing antibody titers, and T cell activation. CD8+ T cell responses showed the strongest correlation with viral load reduction, suggesting that cellular immunity to conserved VP7 could serve as a platform for cross-protection against multiple BTV serotypes.
Conclusions:
These findings highlight the potential of heterologous DNA-adenovirus vaccination as an effective DIVA-compatible strategy for BTV control. By inducing strong and protective immune responses, this approach could improve disease surveillance and management, ultimately reducing the impact of BTV on livestock industries.
