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
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.