RESUMEN
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.
RESUMEN
BACKGROUND: Implementation of the recommended post-exposure prophylaxis by vaccination and specific immunoglobulin therapy for rabies is largely hampered by its high cost and inadequate production. Therefore, the development and availability of an economic preparation of rabies immunoglobulin is a high priority for India, where rabies is a major cause of death. We studied the efficacy of four different adjuvants in raising antibodies to rabies antigen in older, discarded equines. METHODS: Eleven equines, 23-26 years old, were divided into 4 groups to receive four different adjuvants in small amounts (1-2 ml)-Freund complete adjuvant with Mycobacterium tuberculosis, Freund complete adjuvant with M. butyricum, Freund incomplete adjuvant and bentonite--along with purified chick embryo cell vaccine. The immunization schedule was spread over 105 days and the antibody titres were measured on days 56, 91 and 119. RESULTS: On day 119 (third sampling), Freund complete adjuvant with M. tuberculosis provided a geometric mean titre of 654.03 IU/ml in comparison with a titre of 459.19 IU/ml with Freund complete adjuvant with M. butyricum, 630.95 IU/ ml with Freund incomplete adjuvant and 172.18 IU/ml with bentonite. CONCLUSION: Purified chick embryo cell vaccine in combination with Freund complete adjuvant containing M. tuberculosis and Freund incomplete adjuvant were better at eliciting an immune response. The low quantity of adjuvants used possibly helped by causing very few side-effects but without compromising the antibody titres.