A study of Physico-Chemical Interactions between Haemophilus Influenzae Type b and Meningococcus group C Conjugate Vaccines

ABSTRACT

Background: Haemophilus influenzae type b (Hib) and Meningococcal group C (MenC) conjugate vaccines; which protect against otitis media; bacteremia and invasive diseases; including pneumonia and meningitis; are attractive candidates for combination; since they are both administered to infants and children.A Hib-MenC combination booster at 12 mo has recently been introduced in the U.K. Objectives: To rule out the possibility for the individual vaccine components in a Hib-MenC combination to interact; rendering one or both of them less effective; this work assessed whether these two saccharide-protein conjugates; namely; Hib oligosaccharideCRM197 (Cross-Reacting Material 197) and MenC-CRM197; interact in solution. Furthermore an evaluation of the size and integrity of the vaccines was also performed. Methods: HPLC Size-exclusion chromatography (SEC) with UV-adsorption and refractive index detection was performed with a phosphate and non-phosphate saline buffer to characterize the size of Hib and MenC conjugates as individual components or when combined. Results: Hib-CRM197 eluted significantly earlier than MenC-CRM197 in both phosphate-saline and MOPS-saline buffers on a TSK5000 PWXL column.When combined; there was no significant change in their elution. Refractive index monitoring showed no evidence of significant free saccharide or free protein. Conclusions: By size-exclusion chromatography and refractive index detection methods; there was no indication of degradation; and no evidence of significant associative interactions between Hib-CRM197 and MenC-CRM197 in saline-based buffers; pH 7.2