Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use
| Autor: | Rajeev M. Dhere, Eilís Moran, Asha D. Mallya, Fang Gao, Marc LaForce, Lakshmi Khandke, Annamraju D. Sarma, Sameer Manohar Kale, Trusha Desai, Pankaj Sharma, Ida Karin Nordgren, Rory Care, Sushil Patni, Vinay Gavade, Timothy R. Rudd, Sunil Goel, Ian M. Feavers, Mark R. Alderson, Sunil Gairola, Suhas Hattarki, Nikhil Avalaskar, Prashant Bore, Sambhaji Shankar Pisal, Nicola J. Beresford, Neil Ravenscroft, Barbara Bolgiano |
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| Přispěvatelé: | Department of Chemistry, Faculty of Science |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_treatment Neisseria meningitidis immunogenicity medicine.disease_cause Meningococcal disease Article 03 medical and health sciences 0302 clinical medicine adjuvant medicine Immunology and Allergy Potency 030212 general & internal medicine Molecular Biology acetylation nuclear magnetic resonance spectroscopy General Immunology and Microbiology business.industry Immunogenicity Toxoid meningitis medicine.disease Virology glycoconjugates 030104 developmental biology Infectious Diseases polysaccharide Medicine chromatography serum bactericidal African meningitis belt Critical quality attributes business Adjuvant |
| Zdroj: | Pathogens Pathogens, Vol 10, Iss 928, p 928 (2021) Volume 10 Issue 8 |
| ISSN: | 2076-0817 |
| Popis: | Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India. |
| Databáze: | OpenAIRE |
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