A vaccine candidate for eastern equine encephalitis virus based on IRES-mediated attenuation

Area of Science:

• Virology
• Vaccinology
• Molecular Biology

Background:

• Eastern equine encephalitis (EEE) is a severe mosquito-borne viral disease with no approved human vaccine.
• Developing safe and effective live-attenuated vaccines against alphaviruses presents challenges due to their virulence.

Purpose of the Study:

• To engineer a safe, attenuated recombinant eastern equine encephalitis virus (EEEV) for vaccine development.
• To evaluate the virulence, viremia, and protective efficacy of the engineered EEEV in a murine model.

Main Methods:

• Engineered a recombinant EEEV with an inactivated subgenomic promoter and an encephalomyocarditis virus (EMCV)-derived internal ribosomal entry site (IRES) for structural protein expression.
• Assessed vaccine candidate's safety, including virulence and viremia, in a murine model.
• Determined vaccine efficacy by challenging immunized mice with a virulent North American EEEV strain.

Main Results:

• A single subcutaneous immunization with 10(4) infectious units of the engineered EEEV conferred 100% protection against lethal EEEV challenge in mice.
• No signs of disease or viremia were observed in immunized mice post-immunization or post-challenge.
• The engineered EEEV demonstrated significant attenuation and safety in the murine model.

Conclusions:

• The IRES-based attenuation strategy is a viable approach for developing safe and effective vaccines against EEE.
• This method holds potential for creating vaccines against other alphaviral diseases.