N1MΨU-modified mRNA vaccines break the mold in fish by enhancing innate immune activation.

ABSTRACT: Messenger RNA (mRNA) vaccines have revolutionized immunization strategies in mammals, with chemical modifications such as N1-methyl-pseudouridine (N1MΨU) enhancing stability, translation, and reducing innate immune activation. However, the immunological implications of such modifications in non-mammalian species, particularly teleost fish, remain unclear. In this study, we evaluated the innate immune responses elicited by four vaccine platforms: a DNA vaccine, a live attenuated viral hemorrhagic septicemia virus (VHSV), an unmodified mRNA, and an N1MΨU-modified mRNA. All four vaccines encode the G protein of VHSV (G_VHSV) in rainbow trout. Following intramuscular injection, both mRNA vaccine formats induced robust type I interferon (IFN) responses, comparable to those induced by

SUBMITTER: Porter D 

PROVIDER: S-EPMC12934228 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature