Evaluation of meningococcal C oligosaccharide conjugate vaccines by size‐exclusion chromatography/multi‐angle laser light scattering

Jumel, Kornelia; Ho, Mei Mei; Bolgiano, Barbara

doi:10.1042/ba20020066

Cited by 21 publications

(6 citation statements)

References 30 publications

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“…Measurement of the specific refractive indices (dn/dc) of the two conjugates gave similar values (0.235 ml/ g for T5-rEPA and 0.231 ml/ g for T8-rEPA) which were slightly higher than that of the carrier protein (0.206 ml/g). Previous work had also shown that the larger meningococcal group C conjugates also had dn/dc ratios higher than determined for individual PS or proteins, 24 and this result reaffirms the need to determine dn/dc for each sample.…”

Section: Safety Evaluation Of S Aureus Conjugate Vaccinesupporting

confidence: 56%

Preclinical Laboratory Evaluation of a BivalentStaphylococcus aureusSaccharide: Exotoxin A Protein Conjugate Vaccine

Bolgiano²,

Martino³

et al. 2006

Human Vaccines

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A bivalent, unadjuvanted conjugate vaccine composed of Staphylococcus aureus capsular polysaccharides type 5 and 8 (T5 and T8 PS) conjugated to a novel carrier protein, the mutant nontoxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA), has been the subject of recent clinical trials. A program of preclinical laboratory evaluation was carried out in support of the clinical trials conducted by the National Vaccine Evaluation Consortium. This involved physical chemical characterization and limited assessment of toxicity and immunogenicity. The carrier protein showed good stability and its conformation was essentially maintained when conjugated. The T5- and T8-rEPA conjugates were of a size range (1-3 x 10(6) g/ mol) consistent with polysaccharide conjugates. Fluorescence spectroscopy and molecular sizing showed good batch-to-batch consistency. Although all batches of final fill preparations elicited positive immune responses in the mouse model with three schedule doses of 0.25 microg of each T5/8 conjugate per dose, the mouse serum IgG response to T8 PS varied from batch to batch. Storage temperature at 37 degrees C or below or with repetitive temperature fluctuations did not significantly affect the IgG responses to T5 or T8 PS. Storage at 56 degrees C, however, diminished the mouse serum IgG response to T5 PS. The conformation of the conjugated protein and size of the conjugates correlated well with mouse immunogenicity in the thermal stability samples; significant unfolding of the protein and downshifts in molecular size of the conjugate were only observed when stored at 56 degrees C. The relatively high stability of the novel carrier protein when conjugated to large polysaccharides makes this an attractive candidate carrier protein for other conjugate vaccines. When assayed for serum IgG concentration, the bivalent T5/ 8 conjugate was found to evoke an IgG response well over the threshold value of 10 microg/ ml anti-T5 and -T8 IgG established for the ELISA immunogenicity assay.

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Section: Safety Evaluation Of S Aureus Conjugate Vaccinesupporting

confidence: 56%

Preclinical Laboratory Evaluation of a BivalentStaphylococcus aureusSaccharide: Exotoxin A Protein Conjugate Vaccine

Bolgiano²,

Martino³

et al. 2006

Human Vaccines

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“…SEC-MALS/RI/viscosity of Vi polysaccharides in different eluents demonstrated the need to consider column choice and buffers salts to obtain representative recoveries and highlighted the differences that salt composition makes to hydrodynamic size and viscosity (Hitri et al 2019). See also the following examples of other vaccine-relevant oligo-and poly-saccharide components (Jumel et al 2002;Bardotti et al 2008;Harding et al 2012;Lockyer et al 2015).…”

Section: Molecular Size Profiling and Solution Properties Of Glycoconjugate Vaccinesmentioning

confidence: 99%

Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

et al. 2021

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The global spread of enteric disease, the increasingly limited options for antimicrobial treatment and the need for effective eradication programs have resulted in an increased demand for glycoconjugate enteric vaccines, made with carbohydrate-based membrane components of the pathogen, and their precise characterisation. A set of physico-chemical and immunological tests are employed for complete vaccine characterisation and to ensure their consistency, potency, safety and stability, following the relevant World Health Organization and Pharmacopoeia guidelines. Variable requirements for analytical methods are linked to conjugate structure, carrier protein nature and size and O-acetyl content of polysaccharide. We investigated a key stability-indicating method which measures the percent free saccharide of Salmonella enterica subspecies enterica serovar Typhi capsular polysaccharide, by detergent precipitation, depolymerisation and HPAEC-PAD quantitation. Together with modern computational approaches, a more precise design of glycoconjugates is possible, allowing for improvements in solubility, structural conformation and stability, and immunogenicity of antigens, which may be applicable to a broad spectrum of vaccines. More validation experiments are required to establish the most effective and suitable methods for glycoconjugate analysis to bring uniformity to the existing protocols, although the need for product-specific approaches will apply, especially for the more complex vaccines. An overview of current and emerging analytical approaches for the characterisation of vaccines against Salmonella Typhi and Shigella species is described in this paper. This study should aid the development and licensing of new glycoconjugate vaccines aimed at the prevention of enteric diseases.

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“…The resulting conjugate is primarily end-linked, but can also contain cross-linked molecules, albeit to a much lesser extent than conjugates made from randomly activated PS. d DP of OS around 20–47 102 , 103 . e De- O -acetylated OS; perhaps optional if within parentheses.…”

Section: Factors Determining the Glycan Chain Length Of Vaccine Preparationsmentioning

confidence: 99%

Combined effects of glycan chain length and linkage type on the immunogenicity of glycoconjugate vaccines

2021

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The development and use of antibacterial glycoconjugate vaccines have significantly reduced the occurrence of potentially fatal childhood and adult diseases such as bacteremia, bacterial meningitis, and pneumonia. In these vaccines, the covalent linkage of bacterial glycans to carrier proteins augments the immunogenicity of saccharide antigens by triggering T cell-dependent B cell responses, leading to high-affinity antibodies and durable protection. Licensed glycoconjugate vaccines either contain long-chain bacterial polysaccharides, medium-sized oligosaccharides, or short synthetic glycans. Here, we discuss factors that affect the glycan chain length in vaccines and review the available literature discussing the impact of glycan chain length on vaccine efficacy. Furthermore, we evaluate the available clinical data on licensed glycoconjugate vaccine preparations with varying chain lengths against two bacterial pathogens, Haemophilus influenzae type b and Neisseria meningitidis group C, regarding a possible correlation of glycan chain length with their efficacy. We find that long-chain glycans cross-linked to carrier proteins and medium-sized oligosaccharides end-linked to carriers both achieve high immunogenicity and efficacy. However, end-linked glycoconjugates that contain long untethered stretches of native glycan chains may induce hyporesponsiveness by T cell-independent activation of B cells, while cross-linked medium-sized oligosaccharides may suffer from suboptimal saccharide epitope accessibility.

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Evaluation of meningococcal C oligosaccharide conjugate vaccines by size‐exclusion chromatography/multi‐angle laser light scattering

Cited by 21 publications

References 30 publications

Preclinical Laboratory Evaluation of a BivalentStaphylococcus aureusSaccharide: Exotoxin A Protein Conjugate Vaccine

Preclinical Laboratory Evaluation of a BivalentStaphylococcus aureusSaccharide: Exotoxin A Protein Conjugate Vaccine

Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

Combined effects of glycan chain length and linkage type on the immunogenicity of glycoconjugate vaccines

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