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

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, AlPO(4), 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 AlPO(4) was facilitated through the carrier protein, with only weak binding of AlPO(4) to CRM(197) being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM(197) conjugates. This was verified in AlPO(4) formulations containing DTwP–Hib, where the adsorption of TT-conjugated Hib was higher than CRM(197)-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO(4), 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.