Neisseria meningitidis serogroup X polysaccharide as a qualified antigen for multivalent meningococcal conjugate vaccines
- 1Beijing Zhifei Lvzhu Biopharmaceut Co., Ltd.
- 2State Key Laboratory of Drug Regulatory Science, National Health Commission (NHC) Key Laboratory of Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control (NIFDC)
- 3State Key Laboratory of Organic-Inorganic Composites, College of Life Science and Technology, Beijing University of Chemical Technology
Abstract
Background: Meningococcal meningitis remains a severe global health threat to infants, with multivalent vaccination serving as the most effective preventive measure. In 2021, World Health Organization (WHO) released Defeating Meningitis by 2030: A Global Roadmap , highlighting an urgent demand for conjugate vaccines covering an expanded spectrum of meningococcal serogroups. Accordingly, the development of affordable and globally accessible diagnostic and preventive strategies, including protection against Neisseria meningitidis serogroup X (MenX), has become a key public health priority.
Methods: A comprehensive multi-analytical strategy was implemented, incorporating whole-genome sequencing (WGS), electron microscopy, nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), Congo red staining assay, size-exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS), thermogravimetric analysis/derivative thermogravimetry (TGA/DTG), differential scanning calorimetry (DSC), immunodiffusion assays, enzyme-linked immunosorbent assay (ELISA), and serum bactericidal assay, to systematically evaluate the genetic stability of the MenX production strain, alongside the molecular structure, physicochemical properties, antigenicity, and immunogenicity of MenX polysaccharide (MenX PS).
Results: Our study demonstrated the genomic stability of MenX CMCC 29040 strain and characterized the fermentation kinetics of capsular polysaccharide (CPS) throughout fermentation. Formaldehyde inactivation efficiently promoted the release of CPS from the bacteria while preserving bacterial cellular integrity. Furthermore, micro-morphological characterization for the first time directly visualized the optimal particle size range (100–200 nm) and polydispersity profile of purified MenX PS. In aqueous solution, free MenX PS adopted a compact, globular, random-coil conformation without triple-helix structure, exhibiting distinct structural differences compared with membrane anchored CPS. In addition, quantitative thermal analysis established the thermodynamic threshold of MenX PS, confirming a degradation temperature above 170 °C and superior thermal stability relative to Neisseria meningitidis serogroup A polysaccharide (MenA PS). Moreover, quality-qualified MenX PS exhibited specific antigenic reactivity and the MenX PS-tetanus toxoid conjugate (X-TT), prepared via reductive amination conjugation, presented robust immunogenicity and excellent batch-to-batch reproducibility. In vivo immunization confirmed that X-TT elicited high level MenX PS-specific IgG antibody responses and potent complement-dependent serum bactericidal activity.
Conclusion: MenX PS possesses favorable physicochemical properties and specific immunogenic characteristics, supporting its eligibility as a qualified antigen component for the development of multivalent meningococcal conjugate vaccines (MMCVs).
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BibTeX
@article{fu2026neisseria,
title = {{Neisseria meningitidis serogroup X polysaccharide as a qualified antigen for multivalent meningococcal conjugate vaccines}},
author = {Dan Fu and Kang Li and Xianhua Shi and Fangming Zhang and Jia Zheng and Jia Yu and Zhaoyang Xue and Shunkai Gao and Chuanzhen Lu and Ganggang Sun and Ruichuang Qian and Xinxing Long and Wensheng Xie and Lei Gao},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1943863},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1943863/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neisseria meningitidis serogroup X polysaccharide as a qualified antigen for multivalent meningococcal conjugate vaccines
AU - Dan Fu
AU - Kang Li
AU - Xianhua Shi
AU - Fangming Zhang
AU - Jia Zheng
AU - Jia Yu
AU - Zhaoyang Xue
AU - Shunkai Gao
AU - Chuanzhen Lu
AU - Ganggang Sun
AU - Ruichuang Qian
AU - Xinxing Long
AU - Wensheng Xie
AU - Lei Gao
PY - 2026
DA - 2026/10/08
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1943863
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1943863/full
AB - Background: Meningococcal meningitis remains a severe global health threat to infants, with multivalent vaccination serving as the most effective preventive measure. In 2021, World Health Organization (WHO) released Defeating Meningitis by 2030: A Global Roadmap , highlighting an urgent demand for conjugate vaccines covering an expanded spectrum of meningococcal serogroups. Accordingly, the development of affordable and globally accessible diagnostic and preventive strategies, including protection against Neisseria meningitidis serogroup X (MenX), has become a key public health priority. Methods: A comprehensive multi-analytical strategy was implemented, incorporating whole-genome sequencing (WGS), electron microscopy, nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), Congo red staining assay, size-exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS), thermogravimetric analysis/derivative thermogravimetry (TGA/DTG), differential scanning calorimetry (DSC), immunodiffusion assays, enzyme-linked immunosorbent assay (ELISA), and serum bactericidal assay, to systematically evaluate the genetic stability of the MenX production strain, alongside the molecular structure, physicochemical properties, antigenicity, and immunogenicity of MenX polysaccharide (MenX PS). Results: Our study demonstrated the genomic stability of MenX CMCC 29040 strain and characterized the fermentation kinetics of capsular polysaccharide (CPS) throughout fermentation. Formaldehyde inactivation efficiently promoted the release of CPS from the bacteria while preserving bacterial cellular integrity. Furthermore, micro-morphological characterization for the first time directly visualized the optimal particle size range (100–200 nm) and polydispersity profile of purified MenX PS. In aqueous solution, free MenX PS adopted a compact, globular, random-coil conformation without triple-helix structure, exhibiting distinct structural differences compared with membrane anchored CPS. In addition, quantitative thermal analysis established the thermodynamic threshold of MenX PS, confirming a degradation temperature above 170 °C and superior thermal stability relative to Neisseria meningitidis serogroup A polysaccharide (MenA PS). Moreover, quality-qualified MenX PS exhibited specific antigenic reactivity and the MenX PS-tetanus toxoid conjugate (X-TT), prepared via reductive amination conjugation, presented robust immunogenicity and excellent batch-to-batch reproducibility. In vivo immunization confirmed that X-TT elicited high level MenX PS-specific IgG antibody responses and potent complement-dependent serum bactericidal activity. Conclusion: MenX PS possesses favorable physicochemical properties and specific immunogenic characteristics, supporting its eligibility as a qualified antigen component for the development of multivalent meningococcal conjugate vaccines (MMCVs).
SN - 1664-3224
ER -