Preparation And Immunogenicity Research Of Modified Meningococcal Polysaccharide Conjugate Vaccine By β-glucan

Meningococcal disease is an acute respiratory infectious illness caused by neisseria meningitides,which has characteristics such as broad geographical distribution,high fatality rate and drug resistance. However,meningococcal capsular polysaccharide(CPS) is a T cell independent antigen which couldn’t induce immune memory and be used for children.Conjugate carrier protein to CPS could convert it to T cell dependent antigen and induce immune memory,increase the Ig G antibody production and mature antibody affinity.Therefore,it could not only applied to adults,but also children.However,it is still expected to develop new conjugate vaccine of higher immunogenicity consider of their much inoculation dosage and low immunization efficacy.β-Glucan could combined to specific receptor especially CR3 and Dectin-1, affect the secretion of cytokines and trigger intracellular processes.thereby, it could stimulate humoral immunity and cellular immunity.Even though β-glucan has been widely used to enhance the immunogenicity of antigen,the conjugation of adjuvant and co-administration with conjugate vaccine is rarely applied.In the present study,the CPS-TT is produced by conjugation of meningococcal group Y CPS with tetanus toxoid(TT),then,β-glucan was conjugated and co-administration with CPS-TT to generate CPS-TT-G,CPS-TT/G1 and CPS-TT/G2.The Fourier transform infrared spectoscopy,NMR spectroscopy,Dynamic light scattering and high performance liquid chromatography were used to structure analysis for CPS,CPS-TT and CPS-TT-G.The Immunization experiment was to study the immunogenicity.The CPS-specific Ig M titers of CPS is far lower than CPS-TT and CPS-TT-G,which indicated that TT could remarkably increase the CPS-specific Ig M titers.Interestingly,the ratio of Ig G/Ig M for CPS-TT-G is higher than CPS-TT after third injection,which prove that β-glucan could convert the antibody synthesis from Ig M to Ig G.As compared to CPS-TT,Immunization with CPS-TT-G result in an 8.2-fold increase in CPS-specific Ig G titers,It is probably that CPS-TT-G could ensure CPS-TT and β-glucan reach the antigen presenting cells meantime.on the contrary,co-administration with β-glucan led to lower CPS-specific Ig G titers,It maybe because β-glucan could reach the APC much faster than CPS-TT and occupy the B-cell binding site. Therefore,we could assure that β-glucan is an effective strategy to increase the CPS-specific Ig G immunogenicity of the conjugate vaccine.