Characterization and immunogenicity of meningococcal group C conjugate vaccine prepared using hydrazide-activated tetanus toxoid

Vaccine Analysis: Strategies, Principles, and Control

“…For Hib and Mn C, which both contain in-chain diols from ribitol and the exocylic chain, respectively, periodate treatment causes simultaneous depolymerization and yields terminal aldehydes (Anderson et al 1986), whereas for other polysaccharide structures containing several residues per repeating unit, multiple oxidation sites are available and these will be oxidized at different rates depending on the relative orientation of the diols (cis vs. trans) and whether the residue is an alditol, terminal, or branched sugar. Alternatively, the aldehydes generated can be reacted with hydrazide-derivatized proteins as reported for the preparation of meningococcal A and C tetanus toxoid conjugates (Lee et al 2009;Silveira et al 2007). For polysaccharides containing diols that are not available due to the presence of O-acetyl groups (Pn 1) or pyruvate (Pn 4), these substituents can be partially removed prior to periodate treatment (Prasad 2011).…”

“…However, some strategies require prior derivatization of the protein carrier to generate functional groups that will react specifically with active groups on the saccharide intermediate. This approach is also applicable to toxoids and was used by the Meningitis Vaccine Project to improve the coupling of periodateactivated meningococcal group A polysaccharide to TT (Lee et al 2009) and other groups for conjugates in development against Hib (Laferriere et al 2011) and meningococcal group C disease (Silveira et al 2007). In general, such functional groups are introduced by derivatization of protein amino acids side chains such as glutamic/aspartic acid with a bifunctional reagent (e.g., adipic acid dihydrazide or hydrazine) so that a highly nucleophilic hydrazide group becomes available for coupling with the polysaccharide (Schafer et al 2000).…”

Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid

“…These react with aldehydes more rapidly and completely than the ε-amines of lysine [7][8][9][10]. This method was chosen to develop a new Hib conjugate vaccine at The Biovac Institute in South Africa.…”

Development of a group A meningococcal conjugate vaccine,MenAfriVacTM

“…Studies by Silveira et al in Brazil on a group C meningococcal conjugate using the TT-H technology showed that NMR could be used to show disappearance of the reactive aldehyde groups in the activated PS as a result of conjugation. 29 Additional advanced physico-chemical methods for characterization of meningococcal conjugates have been described, including determination of hydrazine content. 25,31 The described conjugation method produces high molecular weight cross-linked lattice structures, due to multiple aldehyde groups on the PS and multiple hydrazide groups on the tetanus toxoid.…”

“…Similar conjugates were produced in Brazil using the group C meningococcal PS, where they achieved 50% yields of conjugated PS. 29 Use of activated PS and TT-H has also been applied to serogroup W135 conjugate vaccines. 30 Lot release testing of the different components of the meningococcal group A conjugate was done in reference to the 2006WHO recommendations for production of group A meningococcal conjugate vaccines.…”