Advances in vaccinia virus-based vaccine vectors, with applications in flavivirus vaccine development

Historically, virulent variola virus infection caused hundreds of millions of deaths. The smallpox pan-demic in human beings has spread for centuries until the advent of the attenuated vaccinia virus (VV) vaccine, which played a crucial role in eradicating the deadly contagious disease. Decades of exploration and utilization have validated the attenuated VV as a promising vaccine vehicle against various lethal viruses. In this review, we focus on the advances in VV-based vaccine vector studies, including construc-tion approaches of recombinant VV, the impact of VV-specific pre-existing immunity on subsequent VV -based vaccines, and antigen-specific immune responses. More specifically, the recombinant VV-based fla-viviruses are intensively discussed. Based on the publication data, this review aims to provide valuable insights and guidance for future VV-based vaccine development. CO 2022 Elsevier Ltd. All rights reserved.