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

Area of Science:

• Virology
• Vaccinology
• Molecular Biology

Background:

• An unprecedented Japanese encephalitis virus genotype IV (JEV GIV) outbreak occurred in Australia in 2022.
• The outbreak affected humans and over 80 pig farms, highlighting the need for effective JEV GIV countermeasures.

Purpose of the Study:

• To design, construct, and evaluate the efficacy of two novel JEV GIV mRNA vaccines.
• To assess the protective potential of JEV GIV mRNA vaccines in a preclinical mouse model.

Main Methods:

• Development of two non-codon-optimized JEV GIV mRNA vaccines encoding the prME protein, differing in signal peptide length (Native vs. Shorter).
• Vaccination of Ifnar-/- mice with 5 µg of mRNA vaccines.
• Assessment of neutralizing antibody responses, viremia reduction, protection against disease, weight loss, and mortality following lethal JEV GIV challenge.

Main Results:

• Both mRNA vaccines conferred significant protection against lethal JEV GIV challenge in mice.
• Vaccines achieved a five to six log reduction in viremia and ≥80% protection against mortality and disease.
• The Shorter vaccine elicited lower neutralizing antibody responses compared to Imojev but demonstrated comparable protection.

Conclusions:

• In-country mRNA vaccine generation is feasible for responding to local viral outbreaks like JEV GIV.
• JEV GIV mRNA vaccines show promise as potentially easier to manufacture, cheaper, and suitable for immunocompromised individuals.
• These findings support the development of mRNA vaccines as a rapid response tool for emerging infectious diseases.