Identification and Development of African Swine Fever virus vaccine Candidates by Reverse Vaccinology

Principal Investigator(s): ,

Purpose

African Swine Fever (ASF) is an acute, highly contagious and one of the most fatal diseases of domestic swine. ASF is caused by infection with African swine fever virus (ASFv), which has been endemic in sub-Saharan Africa since its discovery in 1921 and has spread to other countries throughout the Americas and Europe. ASF is a severe socio-economic concern for countries with commercial swine and there are currently no vaccines available to protect against it. Vaccine development studies have demonstrated the role of ASFV specific antibodies for partial protection; passive transfer of anti-ASFV antibodies delayed the onset of clinical signs but did not protect animals from death. Therefore a successful vaccine strategy may also require elicitation of cellular immune responses. Due to these concerns, effective medical countermeasures to combat or prevent ASFv infection are of paramount importance.

This project focused on the evaluation of reverse vaccinology (RV), for the identification and development of ASFv vaccine candidates. RV was used to identify and rank novel in silico candidates. Candidates, fused to an immunogenic tag, were expressed in the highly safe poxvirus modified vaccinia Ankara (MVA) vaccine vector to enhance cellular immunity. Vaccine candidates were also tested for immunogenicity and safety.

Outcomes and Impacts

This project demonstrated ASFv-specific T cell responses in pigs immunized with recombinant proteins in the MVA platform. These results are supportive of the ability of the defined antigens to confer protection in a prime-boost efficacy study.  This work has broad applications not only for ASFv, but also for support the RV approach for addressing other high-consequence and trans-boundary disease vaccines.