title: Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components.
abstract: The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. 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, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP-Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. 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. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates.
authors.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.
authors.forename: Robert B D
authors.initials: RB
authors.lastname: Otto
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. Electronic address: Karena.Burkin@nibsc.org.
authors.forename: Karena
authors.initials: K
authors.lastname: Burkin
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. Electronic address: m_saba84@yahoo.co.in.
authors.forename: Saba Erum
authors.initials: SE
authors.lastname: Amir
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. Electronic address: Denniscrane55@gmail.com.
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Crane
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. Electronic address: Barbara.Bolgiano@nibsc.org.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bolgiano
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism*; D000327:Adsorption; D000535:Aluminum / Q000032:analysis*; D001428:Bacterial Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D019741:Haemophilus influenzae type b / Q000276:immunology*; D022401:Meningococcal Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D022401:Meningococcal Vaccines; C410218:serogroup C meningococcal conjugate vaccine; D000535:Aluminum
keywords: Adjuvant; Aluminum; Conjugate vaccine; Haemophilus; Meningococcal; Polysaccharide