Designing Stable Bacillus anthracis Antigens with a View to Recombinant Anthrax Vaccine Development

Area of Science:

• Biotechnology
• Vaccinology
• Protein Engineering

Background:

• Anthrax, caused by *Bacillus anthracis*, poses a significant threat to mammals and humans.
• Current anthrax vaccine candidates based on recombinant protective antigen (rPA) suffer from instability due to proteolysis and deamidation.

Purpose of the Study:

• To develop stabilized variants of recombinant anthrax protective antigen (rPA) for enhanced vaccine efficacy.
• To evaluate the stability and antigenicity of modified rPA and its domains when formulated with virus-based particles.

Main Methods:

• Simultaneous modification of rPA by substituting deamidation-prone asparagine residues and inactivating proteolysis sites.
• Assessment of the stability of modified rPA (rPA83m) and its domain fragments (rPA1+2, rPA3+4) under various temperature conditions.
• Evaluation of antigen stability and specificity in compositions with tobacco mosaic virus-based spherical particles (SPs).

Main Results:

• Modified rPA (rPA83m) and its domain fragments (rPA1+2, rPA3+4) demonstrated significantly improved stability.
• Compositions of modified rPA variants with SPs maintained antigenic specificity for over 40 days at +37 °C.
• The modifications effectively addressed proteolysis and deamidation, key limitations of previous rPA-based vaccines.

Conclusions:

• Stabilized rPA variants and their domain fragments offer a promising foundation for next-generation anthrax vaccines.
• The combination of modified rPA antigens with safe and effective SPs enhances antigen stability and longevity.
• These findings pave the way for developing more robust and effective anthrax vaccines.