Comparative studies of conjugated capsular polysaccharide of Neisseria meningitidis serogroup A with outer membrane vesicle of N. meningitidis serogroup B
Abstract number: 1733_586
Siadat S.D., Nourouzian Shamasbi D., Tabaraiee B., Ahmadi H., Behzadiyannejad Q., Najar Peerayeh S., Adibi Motlagh B., Nejati M., Hedayati M.H.
Objective: Many strategies are being explored to manipulate the immune system of humans/animals to fight better against a pathogenic organisms. The incidence of endemic meningitis and the frequency of epidemic meningitis caused by group A Neisseria meningitidis (GAM) are increasing in Africa and Asia. Although GAMP vaccine confers immunity at all ages, the improved immunogenicity of a conjugate and its compatibility with the World Health Organization's extended programme on immunisation offers advantages over GAMP alone. Henceforth, disease caused by serogroup B strains remains an unsolved health problem in many part of the world and the lack of a serogroup B meningococcal vaccine is a serious public health limitation since these strains account for approximately one-third of meningococcal disease in North America and up to 80% in North Europe.
Method: In this study, polysaccharide from Neisseria meningitides serogroup A was purified according to the World Health Organization protocol. Then outer membrane vesicle (OMV) of serogroup B meningococci was also extracted by deoxycholate reagent using ultracentrifuge. Conjugates of group A meningococcal polysaccharide (GAMP) bound to OMV, with adipic acid dihydrazide (ADH) as a linker and 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide (EDAC) as a coupling agent, were synthesized and characterised. The obtained polysaccharide was activated by cyanogens bromide (CNBr) and 1-cyano-4(dimethylamino)pridium tetrafloroborate (CDAP) separately. First ADH with EDAC was bound to GAMP activated with CNBr to form GAMPCNBr AH. Second ADH with EDAC was bound to GAMP activated with CDAP to form GAMPCDAP AH. Then these derivatives were conjugated to OMV by EDAC to form GAMPCNBr AH-OMV and GAMPCDAPAH-OMV.
Result: Thus, GAMPCDAPAH-OMV with immunogenicities improved over that of GAMP have been prepared and standardised. The yields of GAMPCDAPAH-OMV was 45 to 48%. GAMPCDAPAH-OMV was higher than that of the other conjugate (1517%). The glycoconjugates were shown to induce hyperimmunity in rabbits and formed antibodies against the above mentioned conjugates were detected by immune diffusion technique.
Conclusion: The average yield of conjugation should be improved through a useful activating reagent.CDPA seemed to be a more useful activating reagent, because the treated GAMP had a higher molecular weight and content of O-acetyl than other activator(CNBr). Therefore, the development of a A/B bivalent anti-meningococcal vaccine could be a good candidate.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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