Safety and Immunogenicity of Recombinant Adeno-Associated Virus-Vectored African Swine Fever Virus Antigens.

Despite the significant global economic damage caused by African swine fever (ASF) and ongoing developments in the field of specific prevention tools development, safe and effective vaccines are still missing. A critical factor hindering the development of ASF vaccines is the lack of sufficient data on the pathogenesis of the virus, as well as a deep understanding of the virus' evasion strategies from the innate immune system. Of particular interest in the design of candidate vaccines are viral vectors, especially-adeno-associated virus (AAV), which is widely used in gene therapy and is capable of long-term transgene expression in vivo. This study assessed the safety and immunogenicity of recombinant AAV serotype 2 (rAAV2), into the genome of which the ASF virus B646L (p72), E183L (p54), CP530R (pp60), and CP204L (p30) immunodominant genes are integrated. The study design included immunization of pigs with monocistronic and bicistronic constructs based on rAAV2 in different regimens, assessment of the safety and tolerability of a laboratory sample of the vaccine, the biochemical and hematological status of the animals, as well as indicators of humoral and cellular immunity. It was found that rAAV2s in immunizing doses no more than 10 × 10¹¹ viral particles have satisfactory tolerability, promote the formation of virus-specific antibodies that remain at a high level at least until the 180 days of the experiment. It has been proven that the use of bicistronic constructs makes it possible to achieve a similar immune response as when introducing a cocktail of monocistronic constructs, which allows to reduce the vector load on the animal's body. Thus, rAAV2 is a promising platform for the construction of a candidate vaccine against ASF, as it is biologically safe and activates the humoral and cellular immune response, which is extremely important for the formation of a protective immunity.