Enhancing comparative rabies DNA vaccine effectiveness through glycoprotein gene modifications

Area of Science:

• Veterinary Virology
• Immunology
• Molecular Biology

Background:

• Enhancing DNA vaccine efficacy, particularly for single-dose immunization, presents a significant challenge.
• The glycoprotein (G) gene of the rabies virus Evelyn-Rokitnicki-Abelseth (ERA) strain is a target for vaccine development.

Purpose of the Study:

• To investigate the potential of a modified rabies virus glycoprotein gene to enhance DNA vaccine effectiveness.
• To evaluate the immunogenicity and protective efficacy of a single-dose DNA vaccine utilizing the modified gene.

Main Methods:

• The glycoprotein gene of the ERA rabies virus strain was mutated at amino acid 333 (arginine to glutamine).
• Modified and unmodified glycoprotein genes were cloned into DNA vaccines and administered to mice via intramuscular (IM) or intradermal (ID) routes.
• Virus-neutralizing antibody levels and survival rates following rabies virus challenge were assessed.

Main Results:

• A single dose (100 µg) of the modified DNA vaccine administered via the IM route induced virus-neutralizing antibodies by day 30.
• 80% of mice vaccinated with the modified DNA vaccine survived a lethal rabies virus challenge, compared to 0% in unvaccinated controls.
• A single dose (10 µg) via the ID route yielded similar protective results.
• The unmodified glycoprotein DNA vaccine did not induce detectable neutralizing antibodies by day 30.

Conclusions:

• A single-dose DNA vaccine using a modified rabies virus glycoprotein gene demonstrates significant immunogenicity and protective efficacy in mice.
• The mutation at amino acid 333 appears crucial for enhancing vaccine effectiveness.
• This modified gene holds promise as an ideal candidate for improving DNA vaccine performance.