Pravalence Of Factor H Binding Protein In Neisseria Meningitidis In China

Invasive meningococcal disease(IMD)is characterized by meningitis and sepsis with high case fatality rate and poor prognosis.It is caused by Neisseria meningitidis(Nm)and is a serious threat to the health of children and adolescents.According to the composition and structural characteristics of capsular polysaccharide,Nm can be divided into 12 serogroups,among which serogroups A,B,C,W,X and Y(MenA,MenB,MenC,MenW,MenX,and MenY)cause the majority disease worldwide.Capsular polysaccharide vaccines and polysaccharide conjugate vaccines have been well-established to prevent diseases caused by MenACWY infection.However.because of the similarity to the human neural cell adhesion molecule,it is not feasible to be vaccine component for MenB capSsular polysaccharide,which impeded the development of MenB vaccine greatly.There are currently two vaccine strategies for the prevention of MenB infection.One is outer membrane vesicle(OMV)vaccine,the other is recombinant protein vaccine.The OMV vaccines can stimulate strong bactericidal activity against strains expressing the same type of PorA,thus are more suitable to be used for the control of localised clonal outbreaks.There are two recombinant protein MenB vaccines in use,Bexero(?)is a four-component recombinant protein vaccine(4CMenB)including NadA,NHBA,FHbp and the outer membrane vesicle of epidemic strain in New Zealand with PI.7-2,4 PorA.Trumenba(?)is developed by Pfizer and contains lipid-modified v1.55 and v3.45 FHbp.The common component is FHbp,which is of great value for serogroup B meningococcal vaccine.Both vaccines have been approved in some regions of the world to protect people from meningococcal disease caused by MenB.After the epidemics of meningitis caused by MenA and MenC,invasive cases caused byMenW were reported at times in China,and MenB strains were more and more isolated in cases and healthy carriers,with the occasionally case reports caused by MenX and MenY.Neisseria meningitidis circulating in China are composed of a variety of serogroups.However,only the A+C polysaccharide vaccine was included in the routine childhood vaccination programmes,the ACWY quadruple vaccine has not yet been included,there isn’t an effective vaccine for prevention meningococcal infection caused by MenB in China.Therefore,to study the characteristics of Neisseria meningtidis in our country so as to develop a meningococcal vaccine against epidimic Nm strains in China becomes a matter of great concern.In the present study,we first studied the epidemiological status of Neisseria meningitidis and the distribution of FHbp in different countries and regions based on the data of Neisseria meningitidis in PubMLST.Then we studied the typing and distribution of FHbp of 1012 Nm strains with various serogroups collected over the past 60 years in China,strains were collected from 30 provinces/autonomous regions of China and were analyzed to explore the feasibility of FHbp to be the component of meningococcal vaccine against serogroup B or strains irrespective of serogroups in China.There were totally 8934 records about Neisseria meningtidis strains collected from 66 countries all over the world.Information of Neisseria meningitidis strains from Europe was better recorded compared to other regions,and could effectively represent epidemic strains in Europe.The number of strains from Asia and Oceania was too small to be the foundation to estimate the characteristics of epidemic strains and their FHbp in these areas.We found that many countries around the world are faced with the epidemic of MenB.ST-32 and ST-41/44 complex were the most popular genetic strains,FHbp of the ST-32 complex strains was more conserved,most of the strains had v1.1 FHbp,which was identical to the FHbp contained in the Bexero vaccine.Strains of ST-41/44 complex has a higher diversity of FHbp,FHbp variants were different between strains from patients and healthy carriers.The v1.4,v1.15 and v1.13 subvariants were mainly identified among the patient-derived isolates,and v2.19 subvatiant was more identified in the carrier-derived strains.Strains of different serogroups were of various sequence clonal complexes.MenC of ST-11 complex was widespread in Europe,Africa,North America and South America.MenW of ST-11 complex was also widely pravelent in Europe and Africa.Epidemic,and Nm of ST-11 complex is also very diverse in FHbp.The results showed that the fHbp gene of the MenA strains in China all encoded vairant 1(v1)protein,and all the MenW strains encoded v2 protein.79.7%of the MenC strains derived from patients possessed fHbp gene encoding v1 protein and 20.3%of v2 FHbp.But for healthy carrier-derived strains,most MenC strains harbored fHbp gene encoding v2 protein.For MenB strains,v2 FHbp accounted for the most irrespective of serogroups,and carrier-derived strains had a larger ratio for v2 FHbp of 90.8%than that of patient-derived strains,which accounted for 61,9%.Distribution of FHbp tended to be clustered at the level of sequence type of clonal complex.In summary,the wide prevalence ofNm of ST-32 complex and its conservative FHbp(vl.1),laid the foundation for the vl.1 FHbp to be the component of vaccine.The increasing proportion of Nm strains with v3 FHbp also corresponded to the v3.45 as one of the vaccine components.China had a larger proportion of v1 and v2 FHbp,and we should choose appropriate vaccine strategies to develop the meningococcal vaccine.