Merck: HDC-MALS for Pneumococcal Conjugate Vaccine Characterization

Invasive pneumococcal diseases remain a major global health concern.  Pneumococcal capsular polysaccharides are key immunogenic components used in vaccine antigens.  Conjugating these polysaccharides to a carrier protein enhances the immune response, especially in young children, by stimulating a T-cell-dependent response and immunological memory.  The chemical and physical properties of the conjugates directly influence the immunogenicity of pneumococcal conjugate vaccines (PCVs).  Comprehensive analytical characterization is critical for PCV process control and ensuring product quality.  A team from Merck, Rahway, NJ, introduces a novel method, multi-detection hydrodynamic chromatography (HDC-MALS), for characterizing PCVs. PCVs require precise monitoring of their size and molecular weight during development.  The team detailed the optimization of HDC-MALS, comparing it to the traditional size-exclusion chromatography technique.  HDC-MALS offers advantages for analyzing large, heterogeneous conjugates, providing faster run times and effective characterization through molar mass distribution analysis.  The Merck researchers demonstrate the utility of this method for understanding the PCV conjugation process and investigating issues like filtration problems encountered during manufacturing, suggesting its potential for broader application in analyzing complex bioconjugates.

Jia X, Deng JZ, Winters MA, Paulines MJ, Tong W, Cannon E, Biba M, Zhuang P. Characterization of pneumococcal conjugates in vaccine process development by multi-detection hydrodynamic chromatography. J Pharm Biomed Anal. 2025 Aug 15;261:116826. doi: 10.1016/j.jpba.2025.116826. Epub 2025 Mar 20. PMID: 40121703.

https://www.sciencedirect.com/science/article/pii/S0731708525001670