Coming of age: mRNA vaccines for orthoflaviviruses.

Orthoflaviviruses - including dengue, Zika, yellow fever, Japanese encephalitis, and Powassan viruses - are mosquito- and tick-borne members of the family Flaviviridae. Orthoflaviviruses pose major public health threats, with the potential for epidemics and pandemics. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines offer a powerful platform by delivering in vitro-synthesized viral antigen-encoding mRNAs into the host, where they generate proteins that trigger robust immune responses. These synthetic platforms simplify the expression of complex viral glycoproteins, allow rapid and scalable manufacturing that is critical in a pandemic/epidemic scenario, and support multivalent designs to broaden protection. This review highlights recent advancements in mRNA vaccines for orthoflaviviruses and examines how innovations in antigen design and delivery platforms may offer broad, safe, and durable protection against diverse pathogenic orthoflaviviruses.