mRNA vaccines: Emerging opportunities for herpesvirus prevention and therapeutic intervention

Herpesviruses infect over 90 % of the global population, imposing a significant disease burden worldwide. The complex lifecycle of herpesviruses, characterized by both lytic infection and latency, poses substantial challenges to vaccine development. To date, among the nine known human herpesviruses, only varicella-zoster virus (VZV) has a licensed commercial vaccine, leaving an urgent need for novel and broadly protective vaccine strategies against the remaining members of this viral family. mRNA vaccine platforms, which allow in situ expression of high levels of antigenic proteins without the risk of genomic integration, offer promising advantages in safety and immunogenicity. Their success during the COVID-19 pandemic has highlighted their potential for rapid and effective vaccine development. In this review, we first summarize the infection and latency mechanisms of the nine human herpesviruses. We then comprehensively examine recent advances in mRNA vaccine research targeting these viruses, including antigen design, structural optimization, immune protection profiles, and safety assessments. Finally, we discuss current limitations and bottlenecks in herpesvirus vaccine development, with the goal of informing future efforts toward the design of broad-spectrum, safe, and effective herpesvirus vaccines.