ArticleCurrent medical science2023
Optimization of the Process for Preparing Bivalent Polysaccharide Conjugates to Develop Multivalent Conjugate Vaccines against Streptococcus pneumoniae or Neisseria meningitidis and Comparison with the Corresponding Licensed Vaccines in Animal Models.
Article in Current medical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it, 2 citations in OpenAlex.
- Two decades of global research on tetanus vaccines and tetanus immunoglobulins: a comprehensive bibliometric analysis and integrative review (2000-2025).Frontiers in cellular and infection microbiology · 2026Pooled it
- Further Insights into the Measurement of Free Polysaccharide in Meningococcal Conjugate Vaccines.Vaccines · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThis study aimed to describe, optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides (CPs) with tetanus toxoid (TT) as bivalent conjugates.
methodsDifferent molecular weights (MWs) of polysaccharides, activating agents and capsular polysaccharide/protein (CP/Pro) ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk. Using the described method and optimized parameters, a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.
resultsThe immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC, while higher MWs were superior for Pn4-TT-Pn14, Pn6A-TT-Pn6B, Pn7F-TT-Pn23F and Pn8-TT-Pn11A. For activating polysaccharides, 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) was superior to cyanogen bromide (CNBr), but for Pn1, Pn3 and MenC, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC) was the most suitable option. For Pn6A-TT-Pn6B and Pn8-TT-Pn11A, rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses, while for Pn4-TT-Pn14, higher CP/Pro ratio was better. Instead of interfering with the respective immunological activity, our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.
conclusionThe result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines, laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.
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Registered trials
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