A Lipid Nanoparticle-Formulated Self-Amplifying RNA Rift Valley Fever Vaccine Induces a Robust Humoral Immune...

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Rift Valley fever (RVF) is a mosquito-borne zoonotic disease with significant impact on livestock and human health.
• Current RVF vaccines for livestock have limitations in safety and efficacy, and no licensed human vaccine is available.

Purpose of the Study:

• To design and evaluate novel self-amplifying RNA (saRNA) vaccines for Rift Valley fever (RVF).
• To assess the humoral immunogenicity and neutralizing activity of saRNA RVF vaccines in a mouse model.

Main Methods:

• Engineered plasmid DNA encoding Rift Valley fever virus (RVFV) M segment sequences, including enhanced glycoprotein expression variants.
• Cloned sequences into Venezuelan equine encephalitis virus (VEEV) replicons to create saRNA constructs.
• Formulated saRNA in lipid nanoparticles and assessed immunogenicity in BALB/c mice, measuring RVFV Gn-specific IgG antibodies and pseudovirus-neutralizing activity.

Main Results:

• Both wild-type (WT) consensus and furin-T2A derivative saRNA vaccines induced dose-dependent RVFV Gn IgG antibodies in mice.
• Significant RVFV pseudovirus-neutralizing activity was observed in mice immunized with 1 µg or 10 µg of the WT consensus saRNA vaccine.
• The WT consensus saRNA vaccine demonstrated promising immunogenicity.

Conclusions:

• The developed saRNA RVF vaccines are immunogenic in mice.
• The WT consensus saRNA RVF vaccine shows potential and warrants further investigation for RVF prevention.