Background: Neisseria meningitidis is a major global cause of bacterial meningitis and septicemia, especially among infants, adolescents, and young adults. Conjugate vaccines have significantly reduced the burden of invasive meningococcal disease by inducing robust T cell–dependent immune responses and long-term immunological memory. The chemical method used to conjugate capsular polysaccharides to carrier proteins plays a decisive role in determining vaccine immunogenicity, stability, and scalability.
Objectives: This review aims to provide a comparative evaluation of established and emerging polysaccharide–protein conjugation chemistries applied in meningococcal vaccine development, highlighting their chemical mechanisms, advantages, limitations, and implications for vaccine design.
Materials and Methods: A narrative review was conducted using approximately 60 peer-reviewed articles retrieved from PubMed, Scopus, and Web of Science covering the period 2018–2025. Search terms included “meningococcal vaccine”,“polysaccharide-protein conjugation,” “carrier protein,” and “conjugation method”. Relevant studies were selected based on predefined inclusion and exclusion criteria, and data were synthesized narratively and comparatively.
Results: Five major conjugation strategies—reductive amination, carbodiimide-mediated coupling, CDAP activation, thiol–maleimide chemistry, and azide–alkyne cycloaddition—were identified as the principal approaches used in licensed and experimental meningococcal conjugate vaccines. Reductive amination remains popular due to its simplicity and stability, whereas click chemistry and other site-specific methods provide greater structural control, although they require specialized reagents and techniques. Key determinants of vaccine performance include choice of carrier protein, polysaccharide chain length, activation conditions, reaction specificity, and process scalability.
Conclusion: Optimal meningococcal vaccine design requires selecting a conjugation method that achieves the desired balance between immunogenicity, manufacturing feasibility, and regulatory acceptability. Continued innovation in coupling chemistries and carrier protein development will be essential to advance cost-effective, safe, and widely accessible next-generation vaccines.
Type of Study:
Applicable |
Subject:
General Received: 2024/06/30 | Accepted: 2024/06/30 | Published: 2024/06/30