A self-amplifying mRNA vaccine expressing PRV gD induces robust immunity against virulent mutants

Pseudorabies virus (PRV) causes an acute febrile infectious disease of pigs. Since 2011, PRV variants have appeared and spread nationwide in China. mRNA vaccines present a safe alternative and can stimulate humoral and cellular immunity. We constructed a self-amplifying mRNA (saRNA) vaccine containing gD gene of a highly virulent PRV variant. In mice, the PRV saRNA gD vaccine induced high levels of neutralizing antibodies. In piglets, vaccination with the PRV saRNA gD vaccine at a dose of as little as 5 μg induced very strong humoral immunity and cellular immunity, providing full protection against challenge infection with very virulent PRV variants. Protection following vaccination with saRNA gD induced significantly stronger protection than attenuated live vaccines and inactivated vaccines. In addition, our results confirm that a PRV saRNA vaccine expressing only one antigen can induce excellent protection in weaned piglets. Hence, the PRV saRNA gD vaccine might be a very promising substitute for inactivated and live vaccines. Finally, we provide proof-of-concept for the development of self-amplifying mRNA vaccines for members of the Alphaherpesvirinae, including herpes simplex virus 1 and 2 as well as varicella zoster virus.