Genetic characterization and estimated 4CMenB vaccine strain coverage of 284 Neisseria meningitidis isolates causing invasive meningococcal disease in Argentina in 2010-2014.

Meningococcal (Neisseria meningitidis) serogroup B (MenB) strain antigens are diverse and a limited number of strains can be evaluated using the human serum bactericidal antibody (hSBA) assay. The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict the likelihood of coverage for large numbers of isolates by the 4CMenB vaccine, which includes antigens Neisseria adhesin A (NadA), Neisserial Heparin-Binding Antigen (NHBA), factor H-binding protein (fHbp), and Porin A (PorA). In this study, we characterized by whole-genome analyses 284 invasive MenB isolates collected from 2010 to 2014 by the Argentinian National Laboratories Network (52-61 isolates per year). Strain coverage was estimated by gMATS on all isolates and by hSBA assay on 74 randomly selected isolates, representative of the whole panel. The four most common clonal complexes (CCs), accounting for 81.3% of isolates, were CC-865 (75 isolates, 26.4%), CC-32 (59, 20.8%), CC-35 (59, 20.8%), and CC-41/44 (38, 13.4%). Vaccine antigen genotyping showed diversity. The most prevalent variants/peptides were fHbp variant 2, NHBA peptides 24, 21, and 2, and PorA variable region 2 profiles 16-36 and 14. The nadA gene was present in 66 (23.2%) isolates. Estimated strain coverage by hSBA assay showed 78.4% of isolates were killed by pooled adolescent sera, and 51.4% and 64.9% (based on two different thresholds) were killed by pooled infant sera. Estimated coverage by gMATS (61.3%; prediction interval: 55.5%, 66.7%) was consistent with the infant hSBA assay results. Continued genomic surveillance is needed to evaluate the persistence of major MenB CCs in Argentina.

The most common clinical manifestations of invasive meningococcal disease include meningitis and septicemia, which can be deadly, and many survivors suffer long-term serious after-effects. Most cases of invasive meningococcal disease are caused by six meningococcal serogroups (types), including serogroup B. Although vaccines are available against meningococcal serogroup B infection, these vaccines target antigens that are highly diverse. Consequently, the effectiveness of vaccination may vary from country to country because the meningococcal serogroup B strains circulating in particular regions carry different forms of the target vaccine antigens. This means it is important to test serogroup B strains isolated from specific populations to estimate the percentage of strains that a vaccine is likely to be effective against (known as 'vaccine strain coverage'). The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict strain coverage by the four-component meningococcal serogroup B vaccine, 4CMenB, against large numbers of serogroup B strains. In this study, we analyzed 284 invasive meningococcal serogroup B isolates collected between 2010 and 2014 in Argentina. Genetic analyses showed that the vaccine antigens of the isolates were diverse and some genetic characteristics had not been found in isolates from other countries. However, vaccine strain coverage estimated by gMATS was consistent with that reported in other parts of the world and with strain coverage results obtained for a subset via another method, the human serum bactericidal antibody (hSBA) assay. These results highlight the need for continued monitoring of circulating bacterial strains to assess the estimated strain coverage of meningococcal serogroup B vaccines.

Population structure of Neisseria meningitidis ST-9493 identified in Colombian isolates.

INTRODUCTION: Neisseria meningitidis is associated with invasive infections causing high mortality rates. The objective of this study was to describe the population structure of Colombian invasive isolates with ST-9493, a potentially emerging clonal group in the country. METHODS: The complete genomes of 34 invasive isolates of serogroup B with ST-9493 and its variants at one or two loci were sequenced by Illumina to describe the phenotypic and genotypic characteristics of these isolates. RESULTS: The relationship of a clonal group associated with ST-136 CC41/44 was phylogenetically established, identifying two main clades composed of isolates from an outbreak or endemic. The most frequent alleles and peptides included porA 17, porB 44, fHbp 2.24, NHBA 10, and the FetA F5-17 variant. Most of the isolates were susceptible to the antibiotics evaluated. CONCLUSION: This study shows that meningococcal isolates with ST-9493 are an autochthonous clonal group with population dynamics and the capacity to cause endemic and epidemic meningococcal disease in Colombia.

Invasive meningococcal disease in Chile seven years after ACWY conjugate vaccine introduction.

BACKGROUND: A serogroup W (MenW) outbreak in Chile prompted a meningococcal vaccination campaign using tetravalent meningococcal-conjugate vaccines (MCV-ACWY) in children since 2012, followed by its introduction into the National Immunization Program (NIP) in toddlers from 2014. Direct protection was observed, but no indirect effects in other age-groups were evidenced. The aim of this study was to describe invasive meningococcal disease (IMD) cases in Chile between 2009 and 2019, and its trend after the introduction of MCV-ACWYs. METHODS: IMD cases, cumulative incidence per 100,000 inhabitants, CFR, and vaccination uptake were described. Data were obtained from the Public Health Institute and NIP. RESULTS: Overall-IMD cases increased in 2009-2014 period, followed by a decline in 2015-2019, focused in infants, children <5 years and people ≥60 years. Serogroup B (MenB) and MenW alternate its predominance. Median overall incidence was 0.6/100,000, increasing from 0.6/100,000 in 2009 to 0.8/100,000 in 2014, later decreasing to 0.4/100,000 in 2019. Median incidences for MenB, serogroup C (MenC) and Y (MenY) were 0.25/100,000, <0.01/100,000 and <0.01/100,000, respectively. Median MenW incidence was 0.53/100,000, increasing from 0.01/100,000 in 2009 to 0.56/100,000 in 2014, followed by a constant decline to 0.12 in 2019. Infants, children <5 years and adults ≥60 years were affected the most, with median incidences of 9.7, 0.9 and 0.93, decreasing to 1.3, 0.1 and 0.1/100,000 in 2019, respectively. Median overall-CFR was 19%, 7.5% for MenB and 24.5% for MenW. Median MCV-ACWY uptake was 93% CONCLUSION: Overall-IMD, MenW cases and incidence declined since 2015 after the MCV-ACWY introduction, while MenB, MenC and MenY have been stable. MenW incidence declined in all age groups, including non-immunized infants and people >60 years. Further analysis and a longer period of observation are needed to have a more robust conclusion about this epidemiological trend. By 2019, CFR remains high.

Translating meningococcal serogroup B vaccines for healthcare professionals.

INTRODUCTION: Vaccination is an effective strategy to combat invasive meningococcal disease (IMD). Vaccines against the major disease-causing meningococcal serogroups are available; however, development of vaccines against serogroup B faced particular challenges, including the inability to target traditional meningococcal antigens (i.e. polysaccharide capsule) and limited alternative antigens due to serogroup B strain diversity. Two different recombinant, protein-based, serogroup B (MenB) vaccines that may address these challenges are currently available. These vaccines have been extensively evaluated in pre-licensure safety and immunogenicity trials, and recently in real-world studies on effectiveness, safety, and impact on disease burden. AREAS COVERED: This review provides healthcare professionals, particularly pediatricians, an overview of currently available MenB vaccines, including development strategies and evaluation of coverage. EXPERT OPINION: Overall, recombinant MenB vaccines are valuable tools for healthcare professionals to protect patients against IMD. Their development required innovative design approaches that overcame challenging hurdles and identified novel protein antigen targets; however, important distinctions in the approaches used in their development, evaluation, and administration exist and many unanswered questions remain. Healthcare providers frequently prescribing MenB vaccines are challenged to keep abreast of these differences to ensure patient protection against this serious disease.

A critical analysis of serogroup B meningococcal disease burden in Brazil (2001-2015): implications for public health decisions.

The recent licensure of two different serogroup B recombinant protein meningococcal vaccines in Brazil emphasizes the importance of a better knowledge of the real burden of serogroup B meningococcal (MenB) disease to establish evidence-based vaccination policies. We performed an observational, descriptive study, from 2001 to 2015, analyzing the incidence and case fatality rates (CFR) of MenB disease in Brazil, according to age group and region. In the absence of any vaccine use targeting MenB disease, a significant decline of 90% in the overall incidence rates of MenB disease was observed (from 0.55 cases/100,000 habitants in 2001 to 0.05 in 2015), with declines found in all age groups during the study period. The highest incidence rates were consistently observed in infants and children 1-4 year of age, whereas adults ≥ 60 years experienced the highest CFR (33.9%). The proportion of cases with serogroup identified increased from 37.1% in 2001 to 51.5% in 2015. Despite an improvement in recent years, the quality of diagnosis is highly heterogeneous in the diverse regions, presenting important deficiencies that still prevent the possibility of a robust and reliable analysis of the burden of the meningococcal disease in Brazil. Based on the findings of this study and taking in account the unlikely indirect effect associated with the use of the new recombinant serogroup B protein vaccines, infants < 1 year is the age group to be prioritized when considering the implementation of routine immunization programmes with MenB vaccines.

Health impact and cost-effectiveness of introducing the vaccine (Bexsero) against MenB disease into the Brazilian immunization programme.

Invasive meningococcal disease (IMD) is associated with a high mortality and severe sequelae. The aim of the present study was to evaluate the potential cost-effectiveness of the Bexsero vaccine in Brazil. We used a cohort model to compare routine vaccination against MenB disease with no vaccination. Epidemiological and cost estimates were obtained from the Brazilian Health Information System. The cost per disability-adjusted life year (DALY) averted and incremental cost-effectiveness ratio (ICER) was estimated assuming a 3-dose vaccination schedule, at R$90 (£ 20.50) per vaccine dose, 82.0% vaccine efficacy against MenB disease and a vaccine uptake of 90.0%. We estimated that 1,527 MenB cases would be prevented and 78 deaths averted. This strategy would cost R$ 762,381, 000 (£ 174,059,503) with a R$ 4,364,280 (£ 996,410) reduction in disease treatment costs. However, at an ICER of 372,256 (£ 84,990) per DALY averted, a vaccination programme is unlikely to be cost-effective.

Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine.

BACKGROUND: Data on duration of protection against invasive meningococcal disease post-vaccination with the recombinant, 4-component, meningococcal serogroup B vaccine (4CMenB) are limited. We evaluated bactericidal activity persistence in adolescents/young adults up to 7.5 years post-primary vaccination with 4CMenB, and response to a booster dose compared with vaccine-naïve controls. METHODS: This open-label, multicenter study (NCT02446743) enrolled 15-24 year-old-previously vaccinated participants from Canada, Australia (group Primed_4y) 4 years post-priming with 4CMenB (2 doses; 0,1-month schedule), and Chile (Primed_7.5y) 7.5 years after priming with 4CMenB (2 doses; 0,1/0,2/0,6-month schedule) and vaccine-naïve participants of similar age (Naïve_4y and Naïve_7.5y groups). Primed participants received a booster dose; vaccine-naïve participants received 2 catch-up doses of 4CMenB, 1 month apart. We evaluated antibody persistence and immune responses using hSBA in terms of geometric mean titers and percentages of participants with hSBA titers ≥4, the kinetics of bactericidal activity post-booster (previously vaccinated) or post-2 doses (vaccine-naïve), and safety. RESULTS: Antibody levels declined at 4 (Primed_4y) and 7.5 (Primed_7.5y) years post-primary vaccination, but remained higher than in vaccine-naïve participants at baseline (≤44% vs ≤ 13% [fHbp]; ≤84% vs ≤ 24% [NadA]; ≤29% vs ≤ 14% [PorA]) for all vaccine antigens except NHBA (≤81% vs ≤ 79%). One month post-booster and post-second dose, 93-100% of primed and 79-100% of vaccine-naïve participants had hSBA titers ≥4 for all antigens. Kinetics of the antibody response were similar across groups with an early robust response observed 7 days post-booster/second dose. No vaccine-related serious adverse event was reported. CONCLUSION: For all antigens except NHBA, a higher proportion of primed participants had hSBA titers ≥4, at 4 and 7.5 years post-vaccination, compared with vaccine-naïve participants. A more robust immune response after booster compared to a first dose in vaccine-naïve individuals, showed effective priming in an adolescent/young adult population. No safety or new reactogenicity issues were identified.

Coinfección por astrovirus y Neisseria meningitidis serogrupo B en una niña / Coinfection by astrovirus and Neisseria B meningitidis in a girl

La infección meningocócica tiene una elevada morbimortalidad. Las coinfecciones virales han sido descritas, fundamentalmente, por virus herpes y respiratorios. Se presenta una paciente que ingresó al Servicio de Emergencia con convulsión tónico-clónica, hipotensión, taquicardia y escala de Glasgow posterior baja. En la Unidad de Cuidados Intensivos mantuvo alteración del nivel de conciencia y requirió estabilización hemodinámica. Se inició antibioterapia de amplio espectro. La paciente mostró deposiciones líquidas malolientes, sin sangre, que fueron cultivadas y estudiadas mediante reacción en cadena de la polimerasa. El líquido cefalorraquídeo fue normal. Las deposiciones resultaron positivas para astrovirus. Se confirmó, mediante reacción en cadena de la polimerasa en sangre, la presencia de Neisseria meningitidis serogrupo B. Se presenta el primer caso pediátrico de coinfección por astrovirus y Neisseria meningitidis. Este virus debería incluirse entre las causas de coinfección para descartar en caso de clínica abdominal predominante, vómitos o deposiciones líquidas.

Meningococcal infection associates high morbidity and mortality. Viral coinfection has been described mainly with herpes and respiratory virus. We describe a child who suffered a tonic-clonic seizure with hypotension, tachycardia and low Glasgow Coma Scale. She maintained an altered mental status and required hemodynamic stabilization in the Pediatric Intensive Care Unit. Wide spectrum antibiotherapy was initiated. She suffered large and foul-smelling liquid not bloody stools which were cultured and studied by polymerase chain reaction. The cerebrospinal fluid was normal. Later the polymerase chain reaction stools were positive to astrovirus, and the blood polymerase chain reaction was positive to Neisseria meningitidis group B. As far as we know, this is the first case of astrovirus and Neisseria meningitidis coinfection described in children. This virus should be considered as new cause of viral coinfection to discard if unexplained abdominal pain or vomits and liquid stools are observed.

[Coinfection by astrovirus and Neisseria B meningitidis in a girl]. / Coinfección por astrovirus y Neisseria meningitidis serogrupo B en una niña.

Meningococcal infection associates high morbidity and mortality. Viral coinfection has been described mainly with herpes and respiratory virus. We describe a child who suffered a tonic-clonic seizure with hypotension, tachycardia and low Glasgow Coma Scale. She maintained an altered mental status and required hemodynamic stabilization in the Pediatric Intensive Care Unit. Wide spectrum antibiotherapy was initiated. She suffered large and foul-smelling liquid not bloody stools which were cultured and studied by polymerase chain reaction. The cerebrospinal fluid was normal. Later the polymerase chain reaction stools were positive to astrovirus, and the blood polymerase chain reaction was positive to Neisseria meningitidis group B. As far as we know, this is the first case of astrovirus and Neisseria meningitidis coinfection described in children. This virus should be considered as new cause of viral coinfection to discard if unexplained abdominal pain or vomits and liquid stools are observed.

La infección meningocócica tiene una elevada morbimortalidad. Las coinfecciones virales han sido descritas, fundamentalmente, por virus herpes y respiratorios. Se presenta una paciente que ingresó al Servicio de Emergencia con convulsión tónico-clónica, hipotensión, taquicardia y escala de Glasgow posterior baja. En la Unidad de Cuidados Intensivos mantuvo alteración del nivel de conciencia y requirió estabilización hemodinámica. Se inició antibioterapia de amplio espectro. La paciente mostró deposiciones líquidas malolientes, sin sangre, que fueron cultivadas y estudiadas mediante reacción en cadena de la polimerasa. El líquido cefalorraquídeo fue normal. Las deposiciones resultaron positivas para astrovirus. Se confirmó, mediante reacción en cadena de la polimerasa en sangre, la presencia de Neisseria meningitidis serogrupo B. Se presenta el primer caso pediátrico de coinfección por astrovirus y Neisseria meningitidis. Este virus debería incluirse entre las causas de coinfección para descartar en caso de clínica abdominal predominante, vómitos o deposiciones líquidas.

Global epidemiology of serogroup B meningococcal disease and opportunities for prevention with novel recombinant protein vaccines.

BACKGROUND: Meningococcal disease (MD) is a major cause of meningitis and sepsis worldwide, with a high case fatality rate and frequent sequelae. Neisseria meningitidis serogroups A, B, C, W, X and Y are responsible for most of these life-threatening infections, and its unpredictable epidemiology can cause outbreaks in communities, with significant health, social and economic impact. Currently, serogroup B is the main cause of MD in Europe and North America and one of the most prevalent serogroups in Latin America. Mass vaccination strategies using polysaccharide vaccines have been deployed since the 1970s and the use of conjugate vaccines has controlled endemic and epidemic disease caused by serogroups A, C, W and Y and more recently serogroup B using geographically-specific outer membrane vesicle based vaccines. Two novel protein-based vaccines are a significant addition to our armamentarium against N. meningitidis as they provide broad coverage against highly diverse strains in serogroup B and other groups. Early safety, effectiveness and impact data of these vaccines are encouraging. These novel serogroup B vaccines should be actively considered for individuals at increased risk of disease and to control serogroup B outbreaks occurring in institutions or specific regions, as they are likely to save lives and prevent severe sequelae. Incorporation into national programs will require thorough country-specific analysis.

Enfermedad meningocóccica invasora por serogrupo B en dos niños chilenos vacunados contra serogrupos ACWY / Meningococcal invasive disease caused by serogroup B in two Chilean children vaccinated against ACWY serogroups

Invasive meningococcal disease (IMD) by serogroup W has become predominant in Chile since 2012, prompting vaccination with conjugate ACWY. We reported two pediatric cases in patients already vaccinated, which evolved with IMD by serogroup B. This should remind us to keep the alertness with this pathology, despite the current vaccination system in Chile, emphasizing in improve our epidemiological case definition and its diagnosis.

La Enfermedad Meningocóccica Invasora (EMI) por serogrupo W ha llegado a ser predominante en Chile desde el 2012, motivando estrategias de inmunización con vacunas conjugadas contra los serogrupos ACWY. Presentamos dos casos pediátricos de pacientes vacunados contra meningococo ACWY que evolucionaron con EMI por serogrupo B, lo que debe recordarnos la alerta y sospecha de esta patología, inclusive con el esquema de vacunación actual chileno, poniendo énfasis en mejorar nuestra definición epidemiológica de caso sospechoso para optimizar su diagnóstico.

Enfermedad Meningocóccica Invasora: 15 años de Experiencia en un Centro de Referencia

Introducción: La enfermedad meningocóccica ha sido y sigue siendo una causa importante de morbilidad y mortalidad a nivel mundial. Objetivo General: Analizar las características clínicas y epidemiológicas de pacientes con infección meningocóccica invasora hospitalizados en un centro hospitalario de referencia. Materiales y método: Estudio descriptivo, observacional y retrospectivo de revisión de historias clínicas de los pacientes de edad ≤ 15 años ingresados en el Servicio de Pediatría del Instituto de Medicina Tropical con aislamiento o detección de N. meningitidis en sangre, LCR u otro fluido estéril, durante el periodo de enero de 1998 a diciembre de 2013. Resultados: Fueron captados 22 pacientes con enfermedad meningocóccica invasora durante el periodo estudiado (1-2 casos/año), con distribución similar para ambos sexos, predominio de <5 años (73%). 12 pacientes (54%) presentaron meningitis y 10 (45%) meningococcemia. Los síntomas predominantes fueron fiebre (100%) y vómitos (90%). Los signos predominantes fueron signos meníngeos (+) (45%), choque (36%) y púrpura (36%). (32%) requirieron ingreso a Unidad de Cuidados Intensivos. Se halló una letalidad del 13% (3 pacientes), todos con meningococcemia. El B fue el serogrupo predominante, (63%), seguido de los serogrupos C y Y/W135. Durante los últimos 5 años el serogrupo B totalizó las muestras remitidas. La meningococcemia (p=0.09), edad < 5 años (p=0.04), presencia de choque (p ≤ 0.01), síndrome purpúrico (p≤0.01) y Glasgow ≤12 (p=0.02) se asociaron con mayor ingreso a UCI. La plaquetopenia < 100.000 se asoció significativamente a ingreso a UCI (p=0.02). El serogrupo B, el más frecuente en toda la población estudiada, tuvo cierta preponderancia en el grupo de ingreso a UCI (p=0.2). Conclusión: La enfermedad meningocóccica presenta un patrón estable de endemicidad en nuestro país. En nuestro estudio el serogrupo B fue el predominante, y hegemónico en los últimos 5 años. La meningococcemia, edad < 5 años, presencia de choque, síndrome purpúrico y Glasgow ≤12 (p=0.02) se asociaron con mayor gravedad. La vigilancia continua es crucial para guiar las estrategias de prevención y control de la enfermedad meningocóccica

Abstrac Introduction: Meningococcal disease has been and remains an important cause of morbidity and mortality worldwide. Objective: To analyze the clinical and epidemiological characteristics of patients with invasive meningococcal infection hospitalized in a hospital of reference. Materials and Methods: A descriptive, observational and retrospective study of review of medical records of patients of age ≤15 years admitted to the Pediatrics Institute of Tropical Medicine in isolation or detection of N. meningitidis in blood, CSF or other sterile fluid, during the period January 1998 to December 2013. Results: 22 patients were captured with invasive meningococcal disease during the period studied (1-2 cases / year), with similar distribution for both sexes, prevalence of <5 years (73%) of 12 patients (54%) had meningitis and 10. (45%) meningococcemia. The predominant symptoms were fever (100%) and vomiting (90%). The predominant signs were meningeal signs (+) (45%), shock (36%) and purple (36%). (32%) required admission to intensive care unit. A fatality rate of 13% (3 patients), all with meningococcemia was found. The serogroup B was the predominant (63%), followed by serogroups C and Y / W135.Durante the last 5 years serogroup B samples totaled forwarded. Meningococcemia (p = 0.09), age < 5 years (p = 0.04), presence of shock (p ≤ 0.01), purpuric syndrome (p ≤ 0.01) and Glasgow ≤ 12 (p = 0.02) were associated with increased ICU admission. Thrombocytopenia < 100,000 was significantly associated with ICU admission (p = 0.02). Serogroup B, the most common in the entire study population, had some preponderance in the ICU income group (p = 0.2). Conclusion: Meningococcal disease presents a stable pattern of endemic in our country. In our study serogroup B was the predominant and hegemonic in the last 5 years. Meningococcemia, age < 5 years, presence of shock, and Glasgow ≤1 2 purpuric syndrome (p = 0.02) were associated with greater severity. Continued vigilance is crucial to guide prevention strategies and control of meningococcal disease

Cost-effectiveness analysis of a multicomponent meningococcal serogroup B vaccine in hypothetic epidemic situation in a middle-income country.

UNLABELLED: NmenB vaccine (4CMenB) is now available, but studies on the cost-effectiveness of vaccine introduction in a country outbreak situation are lacking. The aim of this study was to evaluate the cost-effectiveness of 4CMenB in the context of a hypothetical epidemic outbreak in Chile. We analyzed the direct and indirect costs of acute disease, sequelae and death for each case of meningococcal disease (MD) based on information obtained during the latest NmenB outbreak in Santiago, Chile, occurring between 1993-1999, with an incidence of 5.9/100,000 inhabitants and a mortality of 7.3%. We analyzed the cost of a mass vaccination campaign, considering one dose of 4CMenB for population between 12 months and 25 y of age and 3 doses for infants. Cost-effectiveness analysis was based on 80% and 92% 4CMenB immunogenicity for individual's bellow and over 12 months respectively. Sensitivity analysis was applied to different vaccine costs. RESULTS: The total cost of the epidemic was USD $59,967,351, considering individual cost of each acute case (USD$2,685), sequelae (USD$2,374) and death (USD $408,086). In Chile, the 4CMenB mass vaccination strategy would avoid 215 cases, 61 sequelae, and 16 deaths per year. The strategy would be cost-effective at a vaccine dose cost ≤ of USD$18. CONCLUSIONS: Implementation of a mass vaccination campaign to control a hypothetical NmenB outbreak in Chile would be cost-effective at a vaccine cost per dose ≤ of USD$18. This is the first report of a cost-effectiveness analysis for use of 4CMenB as a single intervention strategy to control an epidemic outbreak of NmenB.

Identificación In Silico del mimetismo molecular entre Epitopes T de Neisseria meningitidis B y el proteoma humano / In Silico identification of molecular mimicry between T-Cell Epitopes of Neisseria meningitidis B and the human proteome

El objetivo del estudio fue determinar los epítopes T de cuatro de las proteínas antigénicas más frecuentes de la membrana externa de Neisseria meningitidis B e identificar los sitios más relevantes donde existe mimetismo molecular para estos epítopes en seres humanos. Para ello se realizó un estudio in silico (estudios que usan herramientas bioinformáticas) usando las bases de datos SWISS-PROT/TrEMBL SYFPEITHI y FASTA, las cuales se emplearon para la determinación de las secuencias proteicas, la predicción de los epítopes T CD4 y CD8, y la determinación del mimetismo molecular en humanos, respectivamente. Se encontró similitud molecular en varias proteínas humanas presentes en diferentes órganos y tejidos, entre ellos: hígado, piel y epitelios, cerebro, sistema linfático y testículos, destacando las encontradas en estos últimos, ya que ellas mostraron la frecuencia más alta de secuencias miméticas. Este hallazgo ayuda a comprender el éxito de N. meningitidis B para colonizar tejidos humanos, el fracaso de ciertas vacunas contra esta bacteria e incluso ayuda a explicar posibles reacciones autoimmunes asociadas a la infección o vacunación.

The objective of the study was to determine the T-cell epitopes of four of the most frequent antigenic proteins of the outer membrane of Neisseria meningitidis B, and to identify the most relevant sites for molecular mimicry with T-cell epitopes in humans. In order to do so, an in silico study -a type of study that uses bioinformatic tools- was carried out using SWISS-PROT/TrEMBL, SYFPEITHI and FASTA databases, which helped to determine the protein sequences, CD4 and CD8 T-cell epitope prediction, as well as the molecular mimicry with humans, respectively. Molecular similarity was found in several human proteins present in different organs and tissues such as: liver, skin and epithelial tissues, brain, lymphatic system and testicles. Of these, those found in testicles were more similar, showing the highest frequency of mimetic sequences. This finding shed light on the success of N. meningitidis B to colonize human tissues and the failure of certain vaccines against this bacterium, and it even helps to explain possible autoimmune reactions associated with the infection or vaccination.

Persistence of antibodies in adolescents 18-24 months after immunization with one, two, or three doses of 4CMenB meningococcal serogroup B vaccine.

We previously demonstrated the immunogenicity and tolerability of the serogroup B meningococcal vaccine, 4CMenB (Bexsero), in 11-17 y-olds randomized to receive 1, 2, or 3 doses at 1, 2, or 6 mo intervals. Participants in this extension study provided an additional blood sample 18-24 mo after last vaccine dose, to assess persistence of serum bactericidal activity with human complement (hSBA), and to compare with age-matched 4CMenB-naïve controls. In the original study, one month after one 4CMenB dose, 93% of subjects had seroprotective hSBA titers (≥4) against indicator serogroup B strains for individual vaccine antigens (fHbp, NadA and NZOMV), increasing to ~100% after two or three doses. After 18-24 mo, 62-73% of subjects given one dose had titers ≥4 against the three antigens, significantly lower rates than after two (77-94%) or three (86-97%) doses. Only proportions with titers ≥ 4 against NZOMV were significantly different between the two (77%) and three (90%, p < 0.0001) dose groups. These results confirm that two doses of 4CMenB, administered 1 to 6 mo apart, provide good levels of bactericidal activity against serogroup B meningococci, which were sustained at least 18-24 mo in over 64% of adolescents for all three tested vaccine-related antigens.

Aislamiento de cepas invasivas de Neisseria meningitidis serogrupos B y Y en la ciudad de Cumaná, años 2009-2010 / Isolation of invasive strains of neisseria meningitides, serogroups B and Y, in Cumana, 2009-2010

Neisseria meningitidis es agente causal de meningitis y meningococcemia. Se realizó la presente investigación a fin de analizar fenotípicamente las cepas invasivas de N. meningitidis aisladas en Cumaná, estado Sucre. Se incluyó el total de cepas identificadas como N. meningitidis en el laboratorio de bacteriología del Hospital Universitario “Antonio Patricio de Alcalá”, durante los años 2009-2010; provenientes de muestras de líquido cefalorraquídeo (LCR) y sangre (hemocultivos). A cada aislamiento se le determinó la susceptibilidad antimicrobiana y el serogrupo respectivo. Durante el período en estudio se analizaron 10 cepas, de las cuales 5 provenían de LCR. El ensayo de susceptibilidad antimicrobiana reveló que las cepas presentaban sensibilidad a penicilina, cefotaxima, meropenem, rifampicina, ciprofloxacina y cloranfenicol siendo sólo resistentes al trimetoprim/ sulfametoxazol. El serogrupo más frecuente fue el B (8 cepas), aislándose un caso de serogrupo Y. Respecto al grupo etario de los pacientes, de las 10 cepas, 8 provenían de pacientes pediátricos. Este es el primer estudio con cepas de N. meningitidis aisladas en Cumaná, por lo que se hace imprescindible el análisis permanente de las cepas aisladas en la zona, con fines de monitoreo, principalmente, de la susceptibilidad antimicrobiana y los serogrupos circulantes.

Neisseria meningitidis is the causal agent for meningitis and meningococcemia. This research was performed to phenotypically analyze invasive strains of N. meningitidis isolated in Cumana, State of Sucre. The study included all strains identified as N. meningitidis isolated in the bacteriology laboratory at the University Hospital “Antonio Patricio de Alcalá,” during the years 2009-2010, coming from cerebrospinal fluid (CSF) samples and blood cultures. For each isolate, the antimicrobial susceptibility and respective serogroup were determined. During the period of study, 10 strains were analyzed, of which 5 came from CSF. The antimicrobial susceptibility test revealed that the strains showed sensitivity to penicillin, cefotaxime, meropenem, rifampicin, ciprofloxacin and chloramphenicol; they were resistant only to trimethoprim/ sulfamethoxazole. Serogroup B was the most frequent (8 strains); one case of serogroup Y was isolated. Regarding the patient’s ages, of the 10 strains, 8 were found in pediatric patients. This is the first study about strains of N. meningitidis isolated in Cumaná, so it is essential that permanent research regarding the strains isolated in the area is carried out for monitoring purposes, mainly in terms of antimicrobial susceptibility and the circulating serogroups.