Humoral and cellular immune responses induced by serogroup W135 meningococcal conjugate and polysaccharide vaccines.

Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex Ⅱ (MHCⅡ), CD86 and CD40 molecules in mice, whereas PSW135 couldn't. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.

Suspected cluster of Neisseria meningitidis W invasive disease in an elderly care home: do new laboratory methods aid public health action? United Kingdom, 2015.

In 2015, a suspected cluster of two invasive meningococcal disease (IMD) cases of serogroup W Neisseria meningitidis (MenW) occurred in elderly care home residents in England over 7 months; case investigations followed United Kingdom guidance. An incident control team reviewed epidemiological information. Phenotyping of case specimens informed public health action, including vaccination and throat swabs to assess carriage. Whole genome sequencing (WGS) was conducted on case and carrier isolates. Conventional phenotyping did not exclude a microbiological link between cases (case 1 W:2a:P1.5,2 and case 2 W:2a:NT). After the second case, 33/40 residents and 13/32 staff were vaccinated and 19/40 residents and 13/32 staff submitted throat swabs. Two MenW carriers and two MenC carriers were detected. WGS showed that MenW case and carrier isolates were closely related and possibly constituted a locally circulating strain. Meningococcal carriage, transmission dynamics and influence of care settings on IMD in older adults are poorly understood. WGS analyses performed following public health action helped to confirm the close relatedness of the case and circulating isolates despite phenotypic differences and supported actions taken. WGS was not sufficiently timely to guide public health practice.

Plan de acción nacional frente a la emergencia de la cepa W-135 responsable de enfermedad meningocócica invasora en Chile, 2012-2013 / National action plan for the emergence of invasive meningococcal disease in Chile, 2012-2013

Invasive meningococcal disease is challenging for public health, mainly when it manifests with sudden changes in incidence, serogroups and hypervirulent clones that spread in the population, causing great alarm due to its sequelae and often fatal course, a situation that occurred in Chile, starting at week 26 of the year 2012. To face this scenario, an organization of multidisciplinary teams was required, called W-135 Action Plan in Chile, which included sanitary alerts, education, reinforcement of the epidemiological surveillance of suspicious cases, immediate diagnosis through state-of-the-art techniques, blocking of contacts, communication plans, and, from the 42nd week, ON the vaccination campaign was started for children aged from 9-months-old to less than 5 years of age. The vaccination strategy had a great impact on the decrease in incidence (1.3 to 0.1/100,000) and case fatality rate in the vaccinated population (23% to 0%), with a high safety profile, leading to its subsequent inclusion in the national immunization program. The ability to develop molecular, clinical and epidemiological studies allowed us to better understand the situation, supporting public health policy decisions for its control. The W-135 Action Plan implemented by the Ministry of Health in Chile, to manage the outbreak of meningococcal disease by Neisseria meningitidis serogroup W, demonstrated that the coordination of these efforts, through an organized Action Plan, allows the implementation of campaigns at the national level achieving high coverage of risk populations in short periods of time, generating a positive impact on the health of the population.

Pericarditis due to Neisseria meningitidis serogroup W135.

Neisseria meningitidis is a well-recognized cause of bacterial meningitis. Although less common, N. meningitidis can also involve extra-meningeal sites, including the pericardium. The frequency of such extra-meningeal clinical manifestations differs depending on N. meningitidis serogroup. N. meningitidis serogroups C and W135 have been reportedly associated with extra-meningeal meningococcal disease more frequently including pericarditis. In general, meningococcal pericarditis is categorized into three etiologies; primary meningococcal disease, secondary disease due to disseminated meningococcemia, and reactive form as an immunologic complication. Importantly, meningococcal pericarditis can cause massive pericardial effusion with cardiac tamponade that can lead to cardiogenic shock. We report a case of pericarditis due to N. meningitidis serogroup W135 secondary to disseminated meningococcal disease.

Rise in Group W Meningococcal Carriage in University Students, United Kingdom.

MenACWY conjugate vaccination was recently introduced in the United Kingdom for adolescents and young adults to reduce disease from infection by Neisseria meningitidis group W. We conducted a cross-sectional meningococcal carriage study in first-year UK university students. Despite 71% MenACWY vaccine coverage, carriage of group W increased substantially.

Emergency Meningococcal ACWY Vaccination Program for Teenagers to Control Group W Meningococcal Disease, England, 2015-2016.

During the first 12 months of an emergency meningococcal ACWY vaccination program for teenagers in England, coverage among persons who left school in 2015, the first cohort to be vaccinated, was 36.6%. There were 69% fewer group W meningococcal cases than predicted by trend analysis and no cases in vaccinated teenagers.

Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among Invasive Neisseria meningitidis Serogroup W Sequence Type (ST)-11 Strains.

Neisseria meningitidis is an important cause of meningococcal disease globally. Sequence type (ST)-11 clonal complex (cc11) is a hypervirulent meningococcal lineage historically associated with serogroup C capsule and is believed to have acquired the W capsule through a C to W capsular switching event. We studied the sequence of capsule gene cluster (cps) and adjoining genomic regions of 524 invasive W cc11 strains isolated globally. We identified recombination breakpoints corresponding to two distinct recombination events within W cc11: A 8.4-kb recombinant region likely acquired from W cc22 including the sialic acid/glycosyl-transferase gene, csw resulted in a C→W change in capsular phenotype and a 13.7-kb recombinant segment likely acquired from Y cc23 lineage includes 4.5 kb of cps genes and 8.2 kb downstream of the cps cluster resulting in allelic changes in capsule translocation genes. A vast majority of W cc11 strains (497/524, 94.8%) retain both recombination events as evidenced by sharing identical or very closely related capsular allelic profiles. These data suggest that the W cc11 capsular switch involved two separate recombination events and that current global W cc11 meningococcal disease is caused by strains bearing this mosaic capsular switch.

Cluster of serogroup W-135 meningococcal disease in 3 military recruits.

We describe a group of 3 cases of invasive meningococcal disease that occurred in a military training camp in April 2011. All three patients were hospitalized. Ultimately, two patients recovered and one died. One patient had meningitis, one patient had septicemia and meningitis, and the other had no definite septicemia or meningitis. Neisseria meningitidis serogroup W-135 was detected in the serum and cerebrospinal fluid (CSF) of all patients by real-time polymerase chain reaction. In the one case of mortality, two strains were isolated from the patient's blood and CSF. Using multilocus sequence typing analysis, these strains were identified as a novel sequence type, ST-8912. Special attention is required for the meningococcal disease in military camp because the military personnels are in high risk of contact transmission.

Cluster of Serogroup W-135 Meningococcal Disease in 3 Military Recruits

We describe a group of 3 cases of invasive meningococcal disease that occurred in a military training camp in April 2011. All three patients were hospitalized. Ultimately, two patients recovered and one died. One patient had meningitis, one patient had septicemia and meningitis, and the other had no definite septicemia or meningitis. Neisseria meningitidis serogroup W-135 was detected in the serum and cerebrospinal fluid (CSF) of all patients by real-time polymerase chain reaction. In the one case of mortality, two strains were isolated from the patient's blood and CSF. Using multilocus sequence typing analysis, these strains were identified as a novel sequence type, ST-8912. Special attention is required for the meningococcal disease in military camp because the military personnels are in high risk of contact transmission.

Spread of Neisseria meningitidis serogroup W clone, China.

During February 2011-June 2012, invasive infection with Neisseria meningitidis serogroup W was identified in 11 persons in southeastern China. All isolates tested had matching or near-matching pulsed-field gel electrophoresis patterns and belonged to multilocus sequence type 11. The epidemiologic investigation suggested recent transmission of this clonal complex in southeastern China.

Serogroup W135 meningococcal disease, The Gambia, 2012.

In 2012, an outbreak of Neisseria meningitidis serogroup W135 occurred in The Gambia. The attack rate was highest among young children. The associated risk factors were male sex, contact with meningitis patients, and difficult breathing. Enhanced surveillance facilitates early epidemic detection, and multiserogroup conjugate vaccine could reduce meningococcal epidemics in The Gambia.

Caracterización clínica de los casos de enfermedad meningocóccica por serogrupo W135 confirmados durante el año 2012 en Chile / Clinical characterization of cases with meningococcal disease by W135 group in Chile, 2012

Background: During 2012 in Chile, there were 60 cases of serogroup W135 meningococcal disease, which accounts for 57.7% of identified serogroup cases. Aim: To describe main clinical features of patients with serogroup W135 meningococcal disease confirmed in 2012. Material and Methods: Descriptive study of case series based on retrospective review of medical records. Results: Male patients represented 61.7% and 46.7% were children under 5 years. At first clinical attention, 3.4% of patients were suspected of meningococcal disease, while 83.3% had meningococcemia as final diagnosis. Also at first attention, the most common symptoms or clinical signs were fever ≥ 38.0° C (60.3%), cold symptoms (52.5%), and nausea or vomiting (46.7%). Meningeal signs had a low frequency (8.7%). Diarrhea was the second most common symptom found among deceased patients (55.6%) and statistically higher than survivors (26.8%; p = 0.034). Six cases reported with sequelae: limb amputation, hearing loss or neurological damage, and mortality was 31.7%. Discussion: In 2012, serogroup W135 meningococcal disease reported high mortality, atypical clinical presentation, low initial meningococcal disease diagnosis, and a high number of cases with poor clinical course.

Introducción: En el año 2012 en Chile, se presentaron 60 casos de enfermedad meningocóccica (EM) causadas por serogrupo W135, que representa 57,7% de los casos seroagrupables. Objetivo: Describir las características clínicas de los casos de EM por serogrupo W135 confirmados durante el año 2012. Material y Métodos: Estudio descriptivo, de series de casos basada en la revisión de las fichas clínicas. Resultados: El 61,7% de los casos fueron varones y 46,7% tenía menos de 5 años. En la primera consulta, 3,4% tuvo sospecha de EM, en tanto 83,3% tuvo diagnóstico final de meningococcemia. En la primera consulta, los síntomas y/o signos más frecuentes fueron fiebre ≥ 38,0°C (60,3%), cuadro catarral respiratorio (52,5%) y náuseas y/o vómitos (46,7%). Mientras que los signos de irritación meníngea se presentaron en 8,7%. En los fallecidos la diarrea fue el segundo síntoma más frecuente (55,6%), y estadísticamente superior respecto de los sobrevivientes (26,8%; p = 0,034). Seis casos presentaron secuelas: amputaciones de extremidades, hipoacusia o daño neurológico y la letalidad fue de 31,7%. Discusión: la EM por el serogrupo W135 en el año 2012, tuvo una elevada letalidad, presentación clínica inespecífica, sospecha diagnóstica inicial baja y un alto número de casos cursaron con una mala evolución.

Emergencia de la cepa W135 causante de enfermedad meningocócica invasora en Chile 2012 / Emergence of W135 meningococcal serogroup in Chile during 2012

The epidemiologic behavior of the Invasive Meningococcal Disease (IMD) in Chile has changed. At the end of 2011, the W135 serogroup belonging to the hypervirulent clone ST-11 emerged. It affected diverse countries of the world, after the Mecca pilgrimage in 2000. In Chile, there have been 133 IMD cases during 2012. These figures represent an incidence of 0.7 per 100,000 inhabitants, which is 30% higher than expected. Eighty eight percent of cases were confirmed by the National Reference Laboratory at the Chilean Public Health Institute. The serogroup was determined in 103 strains and 58% belonged to the W135 serogroup, surpassing for the first time the B serogroup (37%). The Metropolitan Region concentrated 80% of these cases, and the remaining 20% affected other seven regions of the country. Forty seven percent of cases corresponded to children less than 5 years of age. The predominant clinical presentation of the W135 serogroup was a sepsis in 67% of cases. The fatality ratio of IDM during 2012 was 27%, the highest in the past 20 years. With this information, the Chilean Ministry of Health decreed a sanitary alert and implemented an integrated approach to control and prevent W-135 IDM, denominated "W-135 Action Plan".

Immunogenicity and hereditary stability of Neisseria meningitidis serogroup W135/Y strains used in conjugate vaccine production / 中华微生物学和免疫学杂志

Objective To evaluate the immunogenic stability and hereditary stability of Neisseria meningitides serogroup W135/Y[CMCC(B)29037/CMCC(B)29028]within all the passages,which isolated from china.Methods The toxicity of the 3rd,5th,10th,15th,20th,25th and 30th passage of the Neisseria meningitidis was assayed in mice.Serological detection and biochemical detection were measured,and immunized mice subcutaneously.The antigeeicity of each passage of Neisseria meningitides serogroup W135/Y were measured by serum bactericidal test and the indirect ELISA.With the 30 passage of Neisseria meningitides serogroup W135/Y,the effect to the encephalic tissue was measured in mice.Fermented the Neisseria meningitides serogroup W135/Y with 30 passage and purified the capsular polysaccharide,then analyzed the quality respectively.Results The LD50 of the strains CMCC(B)29037/29028 of each passage was low(LD50 ≥ 109),and all the 30logical detection and all the 30 passage of the two strains were half in the tube agglutination.Glucose and maltose fermentation test were positive.Fructose,sucrose and lactose fermentation test were negative.The GMT of immunogenicity were 1114 and 2229 respectively and all the 30 passage were more than 640 and 1040 respectively.After Immunization with individual 30 passage of the Neisseria meningitides,the titer in serum bactericidal assay(SBA)and indirect ELISA were no difference.The capsular polysaccharide purified from Neisseria meningitides serogroup W135/Y met the quality standard.Conclusion Neisseria meningitides serogroup W135/Y,CMCC(B)29037/29028,used in the manufacture of the meningococcal conjugate vaccine,are stable in the toxicity,antigenicity,immunogenicity.Serological detection and biochemical detection are qulified,and the capsular polysaccharide has met the quality standard.

Recognition of the epidemiological significance of Neisseria meningitidis capsular serogroup W135 in the Rio de Janeiro region, Brazil

Neisseria meningitidis retains its ability to cause endemic and hiperendemic disease in human population living in any environment, as well as localized outbreaks and massive epidemics in civilians and military personnel. In Rio de Janeiro it has been reported in the 1990s as prolonged outbreak of serogroup B and at least one epidemic of serogroup C was well defined, both demanding quick action by the Public Health authorities. We report here the emergence of serogroup W135 meningococcal disease causing endemic and case cluster in Rio de Janeiro during the first years of this new century.

Meningococcal Disease in the Republic of Korea Army: Incidence and Serogroups Determined by PCR

This study was performed to determine the incidence and serogroups of meningococcal disease in the Korean Army. From August 2000 to July 2001, we identified prospective cases in the Korean Army. Meningococcal disease was confirmed by isolation of Neisseria meningitidis or detection of its antigen by latex agglutination from cerebrospinal fluid (CSF) or blood. Polymerase chain reactions (PCRs) were performed in the crgA gene to identify N. meningitidis regardless of its serogroup, and then in orf-2 (serogroup A) and siaD (serogroups B, C, Y, and W135) respectively for serogroup prediction. During the study period, twelve patients (four meningitis and eight septicaemia) were identified. The annual incidence was 2.2 per 100,000 (95% confidence interval, 1.3-3.8) among 550,000 private soldiers. Latex agglutinations were positive to A/C/Y/W135 polyvalent latex, but not to B latex in all patients. PCRs of crgA gene were positive in ten patients, whose samples (2 isolates from CSF, 2 CSFs, and 6 sera) were stored. In PCRs for serogroup prediction, one isolate was serogroup A, and one isolate and two sera were serogroup C. The need for meningococcal vaccination would be considered in the Korean Army through the cost-benefit analysis based on the result of this study.