A Poly-Lysine-Based RBD Mucosal Vaccine Induces Potent Antibody Responses in Mice

Area of Science:

• Vaccinology
• Immunology
• Protein Engineering

Background:

• The COVID-19 pandemic underscored the need for advanced mucosal vaccine strategies.
• Current vaccine approaches require enhancement for effective mucosal immunity.

Purpose of the Study:

• To develop novel mucosal vaccines targeting the SARS-CoV-2 Spike protein's receptor-binding domain (RBD).
• To evaluate the immunogenicity of engineered RBD formulations with poly-lysine and cholera toxin B subunit (CTB).

Main Methods:

• Engineered the RBD with poly-lysine (K10 and K5) to increase positive charge.
• Administered engineered RBD formulations with CTB via pulmonary route in BALB/c mice.
• Assessed antigen-specific antibody responses in serum and bronchoalveolar lavage fluid.

Main Results:

• Pulmonary administration of K10-RBD with CTB induced robust neutralizing antibody titers.
• Sustained high serum IgG antibody titers (>10^4) were observed for six months post-third immunization.
• K5-RBD combined with CTB significantly boosted serum IgG and IgA antibody levels.

Conclusions:

• Poly-lysine modification of RBD, when combined with CTB, effectively stimulates mucosal and humoral immunity.
• These findings provide a foundation for designing subunit mucosal vaccines against SARS-CoV-2.
• The engineered RBD-CTB formulation demonstrates potential for long-term immunity induction.