Aldo Giannozzi

Physicochemical characterisation of glycoconjugate vaccines for prevention of meningococcal diseases.

Bacterial capsular polysaccharides covalently linked to an appropriate carrier protein represent the best tool to induce a protective immune response against a wide range of bacterial diseases, such as meningococcal infections. We describe here the physico-chemical characterisation of glycoconjugate molecules designed to prepare a vaccine against Neisseria meningitidis serogroups A, C, W135 and Y. The use of a selective conjugation chemistry resulted in well characterised, reproducible and traceable glycoconjugate that can be consistently manufactured at large scale. A pool of physical and spectroscopic methods was used to establish glycosylation ratio, identity, molecular weight profiles, integrity of carrier protein and sites of glycosylation, assuring effective and consistent lots of vaccines.

Size fractionation of bacterial capsular polysaccharides for their use in conjugate vaccines.

We have developed a chromatographic method suitable for the fractionation of polysaccharides having a negatively charged group. The method permits the removal of all those polysaccharide fragments having a short sequence and which are likely unsuitable for conjugate vaccine construction. The selected polysaccharide fragments can be used to produce glycoconjugate vaccines containing a restricted saccharide polydispersion. We have applied this chromatographic method to three different antigens, Haemophilus influenzae type b and Neisseria meningitidis group A and group C polysaccharides. The method is easily adapted for manufacturing purposes.

N19 Polyepitope as a Carrier for Enhanced Immunogenicity and Protective Efficacy of Meningococcal Conjugate Vaccines

ABSTRACT N19, a string of human universal CD4 T-cell epitopes from various pathogen-derived antigens, was shown to exert a stronger carrier effect than CRM197 for the induction of anti-group C Neisseria meningitidis capsular polysaccharide (MenC), after immunization of mice with various dosages of N19-MenC or CRM-MenC conjugate vaccines. After two immunizations, the N19-based construct induced anti-MenC antibody and protective bactericidal antibody titers higher than those induced by three doses of the CRM-MenC conjugate and required lower amounts of conjugate. N19-based conjugates are superior to CRM-based conjugates to induce protective immune responses to MenC conjugates.