Peptide mimics of the group B meningococcal capsule induce bactericidal and protective antibodies after immunization

Area of Science:

• Vaccinology
• Microbial pathogenesis
• Immunology

Background:

• Neisseria meningitidis serogroup B (MenB) causes severe infections like sepsis and meningitis in children.
• Current prevention strategies are limited as the MenB capsular polysaccharide (CP) is poorly immunogenic due to its similarity to human polysialic acid.
• Developing a vaccine against MenB is crucial for pediatric public health.

Purpose of the Study:

• To develop immunogenic peptide mimics of non-cross-reactive epitopes on the MenB capsular polysaccharide (CP).
• To evaluate the immunogenicity and efficacy of a lead peptide candidate (9M) in preventing MenB infections.

Main Methods:

• Peptide mimics were selected using phage display libraries based on binding to a protective anti-MenB CP monoclonal antibody (mAb).
• The immunogenicity of peptide 9M was assessed after gene priming and carrier-conjugate boosting.
• Serum bactericidal activity and cross-reactivity with polysialic acid were measured. Efficacy was tested in an infant rat model of MenB bacteremia.

Main Results:

• Peptide 9M induced significant serum bactericidal activity against MenB without cross-reacting with human polysialic acid.
• Immune sera generated against 9M successfully prevented bacteremia in infant rats challenged with MenB.
• The peptide mimic approach successfully generated protective antibodies against MenB.

Conclusions:

• Peptide mimic 9M is a promising candidate for a new, effective, and affordable vaccine against Neisseria meningitidis serogroup B.
• This strategy overcomes the immunogenicity challenges associated with the native MenB capsular polysaccharide.
• Further development of 9M-based vaccines could significantly impact the prevention of MenB disease.