مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Analysis of immunogenicity and purification methods in conjugated polysaccharide vaccines: a new approach in fighting pathogenic bacteria
Analysis of immunogenicity and purification methods in conjugated polysaccharide vaccines: a new approach in fighting pathogenic bacteria
Arya Sheikhi,1Mina Shirmohammadpour,2Nima Mahdei Nasirmahalleh,3Bahman Mirzaei,4,*
1. Department of Microbiology and Virology, Zanjan University of Medical Sciences 2. Department of Microbiology and Virology, Zanjan University of Medical Sciences 3. Department of Medical Biochemistry, School of Medicine, Zanjan University of Medical Sciences 4. Department of Microbiology and Virology, Zanjan University of Medical Sciences
Introduction: Over the past two decades, glycoconjugate vaccines have emerged as a powerful tool in preventing bacterial infections, especially those caused by encapsulated pathogens such as Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. These vaccines function by chemically linking bacterial polysaccharides (PSs), which are poorly immunogenic on their own, to carrier proteins, thereby eliciting robust T-cell-dependent immune responses. This has proven especially beneficial for infants and young children, whose immune systems do not respond adequately to unconjugated PS antigens.
Despite their success, the development of conjugate vaccines remains technically demanding. Challenges include the purification of complex and often delicate capsular polysaccharides, optimization of conjugation strategies to preserve immunogenicity, and the need for scalable, cost-effective processes suitable for low-resource settings. Furthermore, inconsistencies in PS composition and linkage chemistry can affect vaccine efficacy and reproducibility.
This review aims to provide a comprehensive overview of current strategies and technological advances in the purification and conjugation of polysaccharide antigens for vaccine development. By analyzing recent research and industrial practices, this article seeks to highlight key trends, identify ongoing challenges, and explore emerging solutions that can shape the future of bacterial vaccine production.
Methods: This review article was conducted through a comprehensive and systematic literature analysis aimed at exploring the purification strategies and immunogenic mechanisms of conjugated polysaccharide vaccines. Peer-reviewed publications, clinical trial data, and patent literature from the past two decades were analyzed, with a focus on vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis.
Databases including PubMed, Scopus, and Web of Science were searched using combinations of keywords such as “glycoconjugate vaccine,” “polysaccharide purification,” “conjugation methods,” “bacterial capsular polysaccharides,” and “vaccine immunogenicity.” Studies included in this review were selected based on relevance to vaccine development processes, purification technologies, conjugation strategies, and their impact on immunological outcomes.
In addition to research articles, regulatory documents and vaccine case studies were reviewed to ensure inclusion of clinically and industrially validated techniques. The selected literature was critically evaluated to extract comparative insights and trends in biochemical and engineering methods relevant to vaccine development.
Results: The literature reviewed highlights significant advancements in both the purification processes and conjugation techniques for polysaccharide-based vaccines. Multiple studies describe evolving methodologies for improving yield, safety, and scalability of capsular polysaccharide (CPS) purification, especially for Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. These include the shift from phenol-based and ultracentrifugation methods to enzymatic treatment, tangential flow filtration (TFF), diafiltration, and detergent-assisted extraction, which have proven to be safer, more efficient, and more environmentally sustainable.
In terms of conjugation, traditional chemical approaches (e.g., periodate oxidation, CDAP chemistry) remain widely used but are now complemented by site-selective conjugation and bioconjugation strategies using engineered E. coli. These methods enable better control over saccharide-to-protein ratios and improve consistency in immunogenic responses. Newer platforms, such as MAPS and GMMA, further enhance immune stimulation and simplify production.
Clinical and preclinical evidence from the reviewed vaccines (e.g., Quimi-Hib, MenAfriVac, Prevnar, and PCV20) demonstrates that improved purification and conjugation techniques directly correlate with higher immunogenicity, broader protection, and better vaccine accessibility in resource-limited settings.
Conclusion: This review underscores the critical role of biochemical and engineering innovations in the development of effective glycoconjugate vaccines. Enhanced purification techniques have allowed for higher-quality antigen preparation with fewer contaminants, while advances in conjugation—particularly site-selective and bioconjugation technologies—have improved vaccine design and immune response.
These innovations not only enable broader and more effective immunization strategies but also address key challenges such as production scalability, cost reduction, and safety. The integration of synthetic and bioengineered methods holds particular promise for developing next-generation vaccines against a wide array of pathogens.
Continued interdisciplinary research combining immunology, microbiology, and biochemical engineering is essential to optimize current platforms and expand vaccine coverage, particularly in low- and middle-income countries where the burden of infectious diseases remains high.