Quality, immunogenicity and stability of meningococcal serogroup ACWY-CRM197, DT and TT glycoconjugate vaccines. Issue 28 (16th June 2017)

• Record Type: Journal Article
• Authors: Beresford, Nicola J.; Martino, Angela; Feavers, Ian M.; Corbel, Michael J.; Bai, Xilian; Borrow, Ray; Bolgiano, Barbara
• Is Part Of: Vaccine. Volume 35:Issue 28(2017)
• Page Start: 3598
• Page End: 3606
• Publication Date: 2017-06-16
• Subjects: Meningococcal conjugate vaccines -- Stability -- Carrier protein; BC bulk conjugate -- CRM197 cross-reacting material197 -- DT diphtheria toxoid -- FF final fill -- FT freeze thaw -- HPLC high performance liquid chromatography -- HPAEC high-pH anion exchange chromatography -- MenA PS meningococcal serogroup A polysaccharide -- PAD pulsed amperometric detection -- RI refractive index -- SBA serum bactericidal antibody -- SEC size exclusion chromatography -- TT tetanus toxoid -- UV ultraviolet; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.03.066
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Mono- and multi-valent MenC conjugate vaccines had similar immunogenicity in mice. A correlation between size and immune response of MenA conjugates was observed. Meningococcal serogroup A was the most thermo-labile of MenACWY conjugate vaccines. Lyophilization of meningococcal group A containing vaccines is advised. Abstract: A physicochemical and immunological study of the stability of three different meningococcal (Men) ACWY conjugate vaccines was performed to evaluate any patterns of serogroup oligo- or polysaccharide-specific or carrier protein-specific stability that would affect immunogenicity. Critical quality and stability-indicating characteristics were measured, with the study supporting the suitability of both HPLC-SEC and HPAEC-PAD methods to detect changes following inappropriate vaccine storage. All three final products, ACWY-CRM197, -DT and -TT conjugate vaccines had expected quality indicator values and similar immunogenicity in a mouse model (anti-PS IgG and rSBA) when stored at +2–8 °C. When stored at ≥+37 °C, all conjugated carrier proteins and serogroup saccharides were affected. Direct correlations were observed between the depolymerization of the MenA saccharide as evidenced by a size-reduction in the MenA conjugates (CRM197, DT and TT) and their immunogenicity. MenA was the most labile serogroup, followed by MenC; then MenW and Y, which were similar. At high temperatures, the conjugated carrier proteins were prone to unfolding and/or aggregation. The anti-MenC IgG responses of the multivalent conjugate vaccines in mice were equivalent to those observed in monovalent MenC conjugate vaccines, and were independent of the carrier protein. For any newly developing MenACWY saccharide-protein conjugate vaccines, a key recommendation would be to consider the lyophilization of final product to prevent deleterious degradation that would affect immunogenicity.