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1.
Emerg Infect Dis ; 22(1): 75-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26689450

RESUMEN

Among 139 patients with suspected bacterial meningitis in Ethiopia, 2012-2013, meningococci (19.4%) and pneumococci (12.9%) were the major disease-causing organisms. Meningococcal serogroups detected were A (n = 11), W (n = 7), C (n = 1), and X (n = 1). Affordable, multivalent meningitis vaccines for the African meningitis belt are urgently needed.


Asunto(s)
Meningitis Bacterianas/inmunología , Meningitis Meningocócica/inmunología , Vacunas Meningococicas/inmunología , Neisseria meningitidis/aislamiento & purificación , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/aislamiento & purificación , Adolescente , Adulto , Niño , Preescolar , Etiopía , Femenino , Humanos , Masculino , Neisseria meningitidis/inmunología , Streptococcus pneumoniae/inmunología , Adulto Joven
2.
Vaccine ; 32(23): 2722-31, 2014 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-24631075

RESUMEN

Surface-expressed protein antigens such as factor H-binding protein (fHbp), Neisserial adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and Porin protein A (PorA); all express sequence variability that can affect their function as protective immunogens when used in meningococcal serogroup B vaccines like the recently-approved 4CMenB (Bexsero(®)). We assessed the sequence variation of genes coding for these proteins and two additional proteins ("fusion partners" to fHbp and NHBA) in pathogenic isolates from a recent low incidence period (endemic situation; 2005-2006) in Norway. Findings among strains from this panel were contrasted to what was found among isolates from a historic outbreak (epidemic situation; 1985-1990). Multilocus sequence typing revealed 14 clonal complexes (cc) among the 66 endemic strains, while cc32 vastly predominated in the 38-strain epidemic panel. Serogroup B isolates accounted for 50/66 among endemic strains and 28/38 among epidemic strains. Potential strain-coverage ("sequence match") for the 4CMenB vaccine was identified among the majority (>70%) of the endemic serogroup B isolates and all of the epidemic serogroup B isolates evaluated. Further information about the degree of expression, surface availability and the true cross-reactivity for the vaccine antigens will be needed to fully characterize the clinical strain-coverage of 4CMenB in various geographic and epidemiological situations.


Asunto(s)
Adhesinas Bacterianas/genética , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Meningitis Meningocócica/prevención & control , Vacunas Meningococicas/genética , Neisseria meningitidis Serogrupo B/clasificación , Adhesinas Bacterianas/inmunología , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Técnicas de Tipificación Bacteriana , Epidemias , Técnicas de Genotipaje , Humanos , Tipificación de Secuencias Multilocus , Neisseria meningitidis Serogrupo B/genética , Noruega , Filogenia , Porinas/genética , Porinas/inmunología
3.
Lancet Infect Dis ; 13(5): 416-25, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23414709

RESUMEN

BACKGROUND: A novel multicomponent vaccine against meningococcal capsular group B (MenB) disease contains four major components: factor-H-binding protein, neisserial heparin binding antigen, neisserial adhesin A, and outer-membrane vesicles derived from the strain NZ98/254. Because the public health effect of the vaccine, 4CMenB (Novartis Vaccines and Diagnostics, Siena, Italy), is unclear, we assessed the predicted strain coverage in Europe. METHODS: We assessed invasive MenB strains isolated mainly in the most recent full epidemiological year in England and Wales, France, Germany, Italy, and Norway. Meningococcal antigen typing system (MATS) results were linked to multilocus sequence typing and antigen sequence data. To investigate whether generalisation of coverage applied to the rest of Europe, we also assessed isolates from the Czech Republic and Spain. FINDINGS: 1052 strains collected from July, 2007, to June, 2008, were assessed from England and Wales, France, Germany, Italy, and Norway. All MenB strains contained at least one gene encoding a major antigen in the vaccine. MATS predicted that 78% of all MenB strains would be killed by postvaccination sera (95% CI 63-90, range of point estimates 73-87% in individual country panels). Half of all strains and 64% of covered strains could be targeted by bactericidal antibodies against more than one vaccine antigen. Results for the 108 isolates from the Czech Republic and 300 from Spain were consistent with those for the other countries. INTERPRETATION: MATS analysis showed that a multicomponent vaccine could protect against a substantial proportion of invasive MenB strains isolated in Europe. Monitoring of antigen expression, however, will be needed in the future. FUNDING: Novartis Vaccines and Diagnostics.


Asunto(s)
Genes Bacterianos , Meningitis Meningocócica/prevención & control , Vacunas Meningococicas/uso terapéutico , Neisseria meningitidis Serogrupo B/aislamiento & purificación , Adhesinas Bacterianas/análisis , Antígenos Bacterianos/genética , Técnicas de Tipificación Bacteriana/métodos , ADN Bacteriano/análisis , Ensayo de Inmunoadsorción Enzimática , Europa (Continente)/epidemiología , Genotipo , Geografía , Humanos , Meningitis Meningocócica/epidemiología , Meningitis Meningocócica/microbiología , Tipificación de Secuencias Multilocus/métodos , Neisseria meningitidis Serogrupo B/clasificación , Neisseria meningitidis Serogrupo B/genética , Neisseria meningitidis Serogrupo B/patogenicidad , Vigilancia de la Población/métodos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados
4.
Clin Vaccine Immunol ; 19(10): 1609-17, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22875603

RESUMEN

The meningococcal antigen typing system (MATS) sandwich enzyme-linked immunosorbent assay (ELISA) was designed to measure the immunologic cross-reactivity and quantity of antigens in target strains of a pathogen. It was first used to measure the factor H-binding protein (fHbp), neisserial adhesin A (NadA), and neisserial heparin-binding antigen (NHBA) content of serogroup B meningococcal (MenB) isolates relative to a reference strain, or "relative potency" (RP). With the PorA genotype, the RPs were then used to assess strain coverage by 4CMenB, a multicomponent MenB vaccine. In preliminary studies, MATS accurately predicted killing in the serum bactericidal assay using human complement, an accepted correlate of protection for meningococcal vaccines. A study across seven laboratories assessed the reproducibility of RPs for fHbp, NadA, and NHBA and established qualification parameters for new laboratories. RPs were determined in replicate for 17 MenB reference strains at laboratories A to G. The reproducibility of RPs among laboratories and against consensus values across laboratories was evaluated using a mixed-model analysis of variance. Interlaboratory agreement was very good; the Pearson correlation coefficients, coefficients of accuracy, and concordance correlation coefficients exceeded 99%. The summary measures of reproducibility, expressed as between-laboratory coefficients of variation, were 7.85% (fHbp), 16.51% (NadA), and 12.60% (NHBA). The overall within-laboratory measures of variation adjusted for strain and laboratory were 19.8% (fHbp), 28.8% (NHBA), and 38.3% (NadA). The MATS ELISA was successfully transferred to six laboratories, and a further laboratory was successfully qualified.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/normas , Meningitis Meningocócica/inmunología , Vacunas Meningococicas/inmunología , Neisseria meningitidis/inmunología , Adhesinas Bacterianas/inmunología , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Reacciones Cruzadas , Genotipo , Humanos , Meningitis Meningocócica/diagnóstico , Meningitis Meningocócica/prevención & control , Neisseria meningitidis/clasificación , Neisseria meningitidis/genética , Porinas/inmunología , Unión Proteica
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