# mRNA Vaccine Against Japanese Encephalitis Virus Genotype IV Protects Against Lethal Infection

## TL;DR

Researchers developed an mRNA vaccine against Japanese encephalitis virus genotype IV that protected mice from lethal infection and reduced viremia.

## Contribution

The study demonstrates rapid in-country development of an mRNA vaccine for a local JEV GIV outbreak with promising protective efficacy.

## Key findings

- Two mRNA vaccines encoding prME provided ≥80% protection against disease and weight loss in mice.
- Both vaccines reduced viremia by five to six logs and showed significant neutralizing antibody responses.
- The Shorter vaccine induced lower but overlapping antibody responses compared to the approved Imojev vaccine.

## Abstract

In 2022, Australia saw an unprecedented outbreak of Japanese encephalitis virus genotype IV (JEV GIV). The outbreak involved 42 human cases with 7 fatalities, as well as affecting >80 pig farms in New South Wales and Queensland. Herein, we designed, constructed, and tested two JEV GIV mRNA vaccines encoding prME, which provided protection against a lethal JEV GIV challenge in an Ifnar-/- mouse model. The vaccines were not codon optimized and included either the Native (full-length) or a Shorter signal peptide, with the latter missing the N-terminal n-region. Two vaccinations with 5 µg of the Shorter vaccine provided neutralizing antibody responses that were significantly lower but overlapped with those seen after vaccination with Imojev, a live attenuated vaccine approved for use in humans. Both mRNA vaccines provided approximately a five to six log reduction in viremia, ≥80% protection against overt disease and weight loss, and mortality. The paper illustrates in-country mRNA vaccine generation in response to a local outbreak, with JEV mRNA vaccines potentially emerging to be easier to manufacture, cheaper, and more suitable for immunocompromised individuals.