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Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components.

Otto RB, Burkin K, Amir SE, Crane DT, Bolgiano B - Biologicals (2015)

Bottom Line: By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar.At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions.Phosphate ions reduced the binding of the conjugates to the adjuvants.

View Article: PubMed Central - PubMed

Affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. Electronic address: r.bdotto@yahoo.com.

No MeSH data available.


Related in: MedlinePlus

Effect of adjuvant concentration on binding of CRM197 and TT conjugates. The adsorption of (A) MenC-CRM197 and (B) Hib-TT and MenC-TT to aluminum phosphate and aluminum hydroxide were studied as a function of adjuvant concentration. The % adsorption was calculated by measuring the recovery of non-adsorbed protein in the supernatant, relative to controls without adjuvant. The MenC vaccines were in MOPS-saline buffer, pH 7.2 and the Hib-TT was in saline. The target concentration was 20 μg PS/ml. The error bars represent the combined standard uncertainty.
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fig1: Effect of adjuvant concentration on binding of CRM197 and TT conjugates. The adsorption of (A) MenC-CRM197 and (B) Hib-TT and MenC-TT to aluminum phosphate and aluminum hydroxide were studied as a function of adjuvant concentration. The % adsorption was calculated by measuring the recovery of non-adsorbed protein in the supernatant, relative to controls without adjuvant. The MenC vaccines were in MOPS-saline buffer, pH 7.2 and the Hib-TT was in saline. The target concentration was 20 μg PS/ml. The error bars represent the combined standard uncertainty.

Mentions: Fig. 1 shows the adsorption of the MenC-CRM197, MenC-TT and Hib-TT bulk conjugates to aluminum phosphate and aluminum hydroxide in a non-phosphate-containing saline solution at concentrations ranging from 0.06 to 2 mg Al3+/ml. The MenC-CRM197 showed a clear difference in binding to aluminum phosphate, with only 20–40% adsorption of the protein component up to 0.5 mg Al3+/ml, compared to 100% absorption to aluminum hydroxide at the same concentration (panel A). A differential in the adsorption of the two aluminum salts to TT conjugates was not as obvious. It was notable that although the adsorption of both of the TT conjugates (panel B) was titratable at lower concentrations, their adsorption was always greater than 20% even at the lowest concentration used (0.125 mg Al3+/ml).


Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components.

Otto RB, Burkin K, Amir SE, Crane DT, Bolgiano B - Biologicals (2015)

Effect of adjuvant concentration on binding of CRM197 and TT conjugates. The adsorption of (A) MenC-CRM197 and (B) Hib-TT and MenC-TT to aluminum phosphate and aluminum hydroxide were studied as a function of adjuvant concentration. The % adsorption was calculated by measuring the recovery of non-adsorbed protein in the supernatant, relative to controls without adjuvant. The MenC vaccines were in MOPS-saline buffer, pH 7.2 and the Hib-TT was in saline. The target concentration was 20 μg PS/ml. The error bars represent the combined standard uncertainty.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582044&req=5

fig1: Effect of adjuvant concentration on binding of CRM197 and TT conjugates. The adsorption of (A) MenC-CRM197 and (B) Hib-TT and MenC-TT to aluminum phosphate and aluminum hydroxide were studied as a function of adjuvant concentration. The % adsorption was calculated by measuring the recovery of non-adsorbed protein in the supernatant, relative to controls without adjuvant. The MenC vaccines were in MOPS-saline buffer, pH 7.2 and the Hib-TT was in saline. The target concentration was 20 μg PS/ml. The error bars represent the combined standard uncertainty.
Mentions: Fig. 1 shows the adsorption of the MenC-CRM197, MenC-TT and Hib-TT bulk conjugates to aluminum phosphate and aluminum hydroxide in a non-phosphate-containing saline solution at concentrations ranging from 0.06 to 2 mg Al3+/ml. The MenC-CRM197 showed a clear difference in binding to aluminum phosphate, with only 20–40% adsorption of the protein component up to 0.5 mg Al3+/ml, compared to 100% absorption to aluminum hydroxide at the same concentration (panel A). A differential in the adsorption of the two aluminum salts to TT conjugates was not as obvious. It was notable that although the adsorption of both of the TT conjugates (panel B) was titratable at lower concentrations, their adsorption was always greater than 20% even at the lowest concentration used (0.125 mg Al3+/ml).

Bottom Line: By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar.At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions.Phosphate ions reduced the binding of the conjugates to the adjuvants.

View Article: PubMed Central - PubMed

Affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. Electronic address: r.bdotto@yahoo.com.

No MeSH data available.


Related in: MedlinePlus