Could the multicomponent meningococcal serogroup B vaccine (4CMenB) control Neisseria meningitidis capsular group X outbreaks in Africa?
ABSTRACT A new vaccine, 4CMenB, is composed of surface proteins of Neisseria meningitidis and is aimed to target serogroup B (MenB) isolates. The vaccine components are present in meningococcal isolates of other serogroups allowing potential use against meningococcal isolates belonging to non-B serogroups. Isolates of serogroup X (MenX) have been emerged in countries of the African meningitis belt. 4CMenB may offer a vaccine strategy against these isolates as there is no available capsule-based vaccine against MenX. We used the Meningococcal Antigen Typing System (MATS) to determine presence, diversity and levels of expression of 4CMenB antigens among 9 MenX isolates from several African countries in order to estimate the potential coverage of MenX by the 4CMenB vaccine. We performed bactericidal assays against these isolates, using pooled sera from 4CMenB-vaccinated infants, adolescents and adults. The African MenX isolates belonged to the same genotype but showed variation in the vaccine antigens. MATS data and bactericidal assays suggest coverage of the 9 African MenX isolates by 4CMenB but not of two unrelated MenX isolates from France. 4CMenB vaccine can be considered for further investigation to control MenX outbreaks in Africa.
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ABSTRACT: Neisseria meningitidis is responsible for the seasonal burden and recurrent epidemics of meningitis in an area of sub-Saharan Africa known as the meningitis belt. Historically, the majority of the cases in the meningitis belt are caused by serogroup A meningococci. Serogroup C meningococci were responsible for outbreaks in the meningitis belt in the 1980s, while serogroup W (formerly W-135) has emerged as a cause of epidemic meningitis since 2000. Serogroup X meningococci have previously been considered a rare cause of sporadic meningitis, but during 2006-2010, outbreaks of serogroup X meningitis occurred in Niger, Uganda, Kenya,Togo and Burkina Faso, the latter with at least 1300 cases of serogroup X meningitis among the 6732 reported annual cases. While serogroup X has not yet caused an epidemic wave of the scale of serogroup A in 1996-1997 or serogroup W in Burkina Faso during 2002, the existing reports suggest a similar seasonal hyperendemicity and capacity for localised epidemics. Serogroup X incidence appears to follow a pattern of highly localised clonal waves, and in affected districts, other meningococcal serogroups are usually absent from disease. Currently, no licensed vaccine is available against serogroup X meningococci. Following the introduction of a monovalent serogroup A conjugate vaccine (MenAfriVac(®)) in the meningitis belt and the upcoming introduction of pneumococcal conjugate vaccines, vaccine-based prevention of serogroup X may become a public health need. The serogroup X polysaccharide capsule is the most likely target for vaccine development, but recent data also indicate a potential role for protein-based vaccines. A multivalent vaccine, preferably formulated as a conjugate vaccine and covering at least serogroups A, W, and X is needed, and the efforts for vaccine development should be intensified.Vaccine 04/2013; 31(27). DOI:10.1016/j.vaccine.2013.04.036 · 3.49 Impact Factor
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ABSTRACT: Neisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genus Neisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA), and N. meningitidis adhesin A (NadA), have been described as antigens protective against N. meningitidis of serogroup B, and they have been employed as vaccine components in preclinical and clinical studies. In the vaccine formulation, fHbp and NHBA were fused to the GNA2091 and GNA1030 proteins, respectively, to enhance protein stability and immunogenicity. To determine the possible impact of vaccination on commensal neisseriae, we determined the presence, distribution, and conservation of these antigens in the available genome sequences of the genus Neisseria, finding that fHbp, NHBA, and NadA were conserved only in species colonizing humans, while GNA1030 and GNA2091 were conserved in many human and nonhuman neisseriae. Sequence analysis showed that homologous recombination contributed to shape the evolution and distribution of both NHBA and fHbp, three major variants of which have been defined. fHbp variant 3 was probably the ancestral form of meningococcal fHbp, while fHbp variant 1 from N. cinerea was introduced into N. meningitidis by a recombination event. fHbp variant 2 was the result of a recombination event inserting a stretch of 483 bp from variant 1 into the variant 3 background. These data indicate that a high rate of exchange of genetic material between neisseriae that colonize the human upper respiratory tract exists.IMPORTANCE The upper respiratory tract of healthy individuals is a complex ecosystem colonized by many bacterial species. Among these, there are representatives of the genus Neisseria, including Neisseria meningitidis, a major cause of bacterial meningitis and sepsis. Given the close relationship between commensal and pathogenic species, a protein-based vaccine against N. meningitidis has the potential to impact the other commensal species of Neisseria. For this reason, we have studied the distribution and evolutionary history of the antigen components of a recombinant vaccine, 4CMenB, that recently received approval in Europe under the commercial name of Bexsero®. We found that fHbp, NHBA, and NadA can be found in some of the human commensal species and that the evolution of these antigens has been essentially shaped by the high rate of genetic exchange that occurs between strains of neisseriae that cocolonize the same environment.mBio 04/2013; 4(3). DOI:10.1128/mBio.00163-13 · 6.88 Impact Factor
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ABSTRACT: BACKGROUND: Epidemics of meningococcal meningitis occur periodically in the African 'meningitis belt' and are mainly, but not only, due to serogroup A. METHODS: We tested a dipstick as a rapid detection test (RDT) to detect serogroup A using 401 cerebrospinal fluid (CSF) samples. RESULTS: The detection limits were 10(5) CFU/ml with sensitivity and specificity for detecting serogroup A in CSF samples of 88% and 99%, respectively. CONCLUSIONS: The new RDT can be used in field surveillance of meningococcal meningitis to help characterize meningitis cases particularly after introduction of the conjugate vaccine against serogroup A.Transactions of the Royal Society of Tropical Medicine and Hygiene 05/2013; 107(7). DOI:10.1093/trstmh/trt041 · 1.93 Impact Factor