Assessment of the stability and immunogenicity of meningococcal oligosaccharide C-CRM197 conjugate vaccines

Citation
Mm. Ho et al., Assessment of the stability and immunogenicity of meningococcal oligosaccharide C-CRM197 conjugate vaccines, VACCINE, 19(7-8), 2000, pp. 716-725
Citations number
17
Categorie Soggetti
Veterinary Medicine/Animal Health",Immunology
Journal title
VACCINE
ISSN journal
0264410X → ACNP
Volume
19
Issue
7-8
Year of publication
2000
Pages
716 - 725
Database
ISI
SICI code
0264-410X(20001122)19:7-8<716:AOTSAI>2.0.ZU;2-F
Abstract
In this stability study, meningococcal C-CRM197 conjugate vaccines from two different manufacturers that differ in oligosaccharide chain length, numbe r of conjugation sites, conjugation chemistry, manufacturing process and fo rmulation were used. Both the bulk concentrated and final fill preparations were incubated at - 20, 4, 23, 37 or 55 degreesC for 5 weeks or subjected to ten cycles of freeze-thawing. The structural stability, hydrodynamic siz e and integrity of the treated vaccines were monitored by size exclusion ch romatography (FPLC-SEC), high performance anion exchange chromatography cou pled with pulsed amperometric detection (HPAEC-PAD) and fluorescence spectr oscopy techniques. The data showed that the structural stability of the oli gosaccharide chains and of the protein carrier varied between the two conju gates. The experimental immunogenicity was not severely affected by repeate d freeze-thawing, incubation at - 20 or 4 degreesC, but one developed confo rmational changes in the protein carrier when incubated at 23 degreesC or a bove, although the integrity of the oligosaccharide structure was maintaine d. This was not associated with any reduction in primary IgG or ISM antibod y responses to meningococcal C polysaccharide. In the other conjugate vacci ne, exposure to 55 degreesC resulted in the release of a substantial propor tion of free saccharide that was accompanied by significant reduction in bo th IgG and IgM antibody responses to immunisation in the model system. In c onclusion, the two meningococcal C-CRM197 conjugate vaccines were stable wh en stored at the recommended temperatures, although their structural stabil ity and subsequent immunogenicity were influenced by their conjugation chem istry and formulation. (C) 2000 Elsevier Science Ltd. All rights reserved.