Rationally designed minimized TbpB confers broad protection against meningococcal infection

Area of Science:

• Vaccinology
• Structural Biology
• Immunology

Background:

• Transferrin binding protein B (TbpB) is a vaccine candidate against pathogenic Neisseria species.
• Antigenic variability of TbpB complicates the development of broadly protective vaccines.
• Minimizing TbpB by removing variable surface loops focuses immune responses to conserved regions.

Purpose of the Study:

• To develop a minimized TbpB immunogen with enhanced cross-protective capabilities.
• To assess the structural integrity and immunogenicity of the engineered TbpB variant.
• To evaluate the protective efficacy of the minimized TbpB against Neisseria infections in mouse models.

Main Methods:

• Structure-informed antigen engineering to create a "loopless C-lobe" variant of TbpB.
• Structural characterization and stability studies of the engineered protein.
• Murine immunization and challenge studies using Neisseria meningitidis infection models.

Main Results:

• The "loopless C-lobe" demonstrated structural integrity and stability.
• Immunization with the loopless C-lobe elicited robust protective efficacy in mouse models.
• The loopless C-lobe provided broader cross-protection against diverse Neisseria strains compared to intact TbpB.

Conclusions:

• Structure-informed antigen engineering is effective for developing broadly protective protein-based vaccines.
• The minimized "loopless C-lobe" of TbpB is a promising immunogen for vaccines targeting Neisseria.
• This approach overcomes challenges posed by TbpB's antigenic variability.