Neisseria Meningitidis Carriage Research Articles

Variable disruption of epithelial monolayers by Neisseria meningitidis carriage isolates of the hypervirulent MenW cc11 and MenY cc23 lineages.

Colonization of mucosal tissues by Neisseria meningitidis requires adhesion mediated by the type IV pilus and multiple outer-membrane proteins. Penetration of the mucosa and invasion of epithelial cells are thought to contribute to host persistence and invasive disease. Using Calu-3 cell monolayers grown at an air-liquid interface, we examined adhesion, invasion and monolayer disruption by carriage isolates of two clonal complexes of N. meningitidis. Carriage isolates of both the serogroup Y cc23 and the hypervirulent serogroup W cc11 lineages exhibited high levels of cellular adhesion, and a variable disruption phenotype across independent isolates. Inactivation of the gene encoding the main pilus sub-unit in multiple cc11 isolates abrogated both adhesive capacity and ability to disrupt epithelial monolayers. Contrastingly, inactivation of the phase-variable opa or nadA genes reduced adhesion and invasion, but not disruption of monolayer integrity. Adherence of tissue-disruptive meningococci correlated with loss of staining for the tight junction protein, occludin. Intriguingly, in a pilus-negative strain background, we observed compensatory ON switching of opa genes, which facilitated continued adhesion. We conclude that disruption of epithelial monolayers occurs in multiple meningococcal lineages but can vary during carriage and is intimately linked to pilus-mediated adhesion.

Prevalence and Characteristics of Carriage of Neisseria meningitidis Among Young Israeli Adults.

BackgroundNo updated data currently exist regarding Neisseria meningitidis carriage and genomic epidemiology among young Israeli adults.MethodsOropharyngeal swabs were collected from 1801 military recruits on the day of recruitment during 2019. Neisseria meningitidis was detected and identified by culture and quantitative polymerase chain reaction (qPCR). Confirmed isolates were serotyped by qPCR, and encapsulated strains underwent whole-genome sequencing. Risk factors for carriage were determined by analyzing focused questionnaires using uni- and multivariate models. Genomic typing was performed by means of core genome multilocus sequence typing.ResultsCarriage rates overall and of encapsulated strains were 20.1% and 6.7%, respectively. Genogroups B (49.2%) and Y (26.7%) were the most commonly encapsulated strains. Genogroups C, W, and X were scarce, and genogroup A was absent. The most notable clonal complexes (CCs) were CC23 (n = 30), CC32 (n = 16), and CC44/41 (n = 9). Carriage was significantly associated with smoking (odds ratio [OR], 1.82; 95% CI, 1.43–2.33) and boarding school attendance before recruitment (OR, 1.49; 95% CI, 1.14–1.96).ConclusionsThe prevalence of meningococcal carriage among young Israeli adults is high, compared with similar studies in other developed countries. This might be due to sociocultural characteristics including smoking and boarding school attendance during and after high school. The dominant genogroups and CCs found were compatible with those implicated in invasive disease in Israel.

Neisseria meningitidis carriage rate, antibiotic susceptibility profile, and associated factors among prisoners at Jimma zonal correction facility in Jimma Town, Southwestern Ethiopia: a cross-sectional study

BackgroundNeisseria meningitidis causes severe life-threatening meningococcal disease with a case fatality rate of 10–15% even with proper treatment. In Ethiopia, particularly in our study area, inadequate information is found on meningococcal disease. So, this study aimed to assess N. meningitidis carriage rate, antibiotic susceptibility profile, and associated factors among prisoners in Jimma Town, Southwestern Ethiopia.MethodsA cross-sectional study was conducted in Jimma town, Southwest Ethiopia, from May to October 2019. A stratified sampling technique was used and proportional allocation was done. A total of 550 oropharyngeal swabs were collected, processed, isolated, and identified N. meningitidis using standard microbiological techniques. Antibiotics susceptibility test was done for isolates using the disk diffusion method. Data on demographic and associated factors for carriage were collected using a structured questionnaire. Data were summarized using frequency, percentage, graph, and table. A logistic regression model was used to see the association between the dependent and independent variables. Variables with a p-value < 0.25 during bivariate analysis were included in multivariate analysis to identify factors significantly associated with the meningococcal carriage and, a p-value < 0.05 was considered statistically significant.ResultOut of the 550 study participants, 76(13.8%) with (CI: 7.20–18.20) were found carriers of N meningitidis. The predominant isolates were non-serogroupable 26(34.2%) and serogroup W/Y 22(28.9%), respectively. N. meningitidis isolates showed highest sensitivity to chloramphenicol 74(97.4%). Meningococcal carriage rate was significantly associated with being age group of 16–20 years; having respiratory symptoms within 3 months and active cigarette smoking within 3 months.ConclusionsThe majority of participants harbor most of the serogroups responsible for invasive cases of meningococcal disease. Respiratory symptoms, active cigarette smoking, and age group of 16–20 years increased the risk of N. meningitidis pharyngeal carriage rate. This study suggests providing better health education to control respiratory symptoms, smoking, and providing antibiotic prophylaxis for prisoners.

Nasopharyngeal Meningococcal Carriage among Children and Adolescents in Turkey in 2018: An Unexpected High Serogroup X Carriage.

Meningococcal carriage studies and transmission modeling can predict IMD epidemiology and used to define invasive meningococcal disease (IMD) control strategies. In this multicenter study, we aimed to evaluate the prevalence of nasopharyngeal Neisseria meningitidis (Nm) carriage, serogroup distribution, and related risk factors in Turkey. Nasopharyngeal samples were collected from a total of 1267 children and adolescents and were tested with rt-PCR. Nm carriage was detected in 96 participants (7.5%, 95% CI 6.1–9.0), with the peak age at 13 years (12.5%). Regarding age groups, Nm carriage rate was 7% in the 0–5 age group, was 6.9%in the 6–10 age group, was 7.9% in the 11–14 age group, and was 9.3% in the 15–18 age group. There was no statistically significant difference between the groups (p > 0.05). The serogroup distribution was as follows: 25% MenX, 9.4% MenA, 9.4% MenB, 2.1% MenC, 3.1% MenW, 2.1% for MenY, and 48.9% for non-groupable. The Nm carriage rate was higher in children with previous upper respiratory tract infections and with a high number of household members, whereas it was lower in children with antibiotic use in the last month (p < 0.05 for all). In this study, MenX is the predominant carriage strain. The geographical distribution of Nm strains varies, but serogroup distribution in the same country might change in a matter of years. Adequate surveillance and/or a proper carriage study is paramount for accurate/dynamic serogroup distribution and the impact of the proposed vaccination.

Internal Quality Control of Neisseria Meningitidis Carriage in Kaya and Boussouma Region of Center-North Burkina Faso from 2016 to 2017

Internal Quality Control of Neisseria Meningitidis Carriage in Kaya and Boussouma Region of Center-North Burkina Faso from 2016 to 2017

Analysis of Neisseria Meningitidis carriage characteristics among healthy population in Shandong province from 2008 to 2020

Objective: To analyze the carriage characteristics of Neisseria meningitidis (Nm) among healthy population of epidemic cerebrospinal meningitis in Shandong province. Methods: From April 2008 to April 2020, a total of 16 848 healthy population were recruited from Lixia District of Jinan City, Gaomi City of Weifang City, Jiaxiang County of Jining City, Wendeng District of Weihai City, Tancheng County of Linyi City and Linyi County of Dezhou City for the investigation.Throat swab samples were collected, Nm was isolated, cultured and identified, and Nm carrying characteristics of healthy population with different characteristics were analyzed. Results: Among the 16 848 healthy population, male accounted for 51.86% (8 737). A total of 136 Nm strains were isolated, and the carriage rate was 0.81%. Among the 136 Nm strains, serogroup B (60.29%) and ungroupable strains (23.53%) were dominant. Analysis of the Nm carriage rate, that were higher in the healthy population of Linyi (1.39%) and Jinan (1.14%), higher in 13-16 years old (1.60%) and 17-19 years old (1.10%) healthy population, and higher in male (1.02%). Conclusion: The Nm carriage rate of healthy population is relatively low in Shandong Province, and the proportion of serogroup B and ungroupable Nm is relatively high.

Impact of Meningococcal B Vaccine on Invasive Meningococcal Disease in Adolescents.

From 2017, a statewide cluster randomized trial was conducted in South Australia to assess the impact of the meningococcal B vaccine 4CMenB on pharyngeal Neisseria meningitidis carriage in adolescents. Senior schools were randomized to receive the vaccine in 2017 (intervention) or 2018 (control). In this study we report the vaccine impact of 4CMenB on serogroup B invasive meningococcal disease (IMD) in 16- to 19-year-old adolescents in South Australia. This observational time series analysis of serogroup B IMD cases compares the 14 years prior to the commencement of the trial (2003-2016) with the 2 years following 4CMenB vaccination of the 2017 adolescent cohort. Approximately 62% of year 10 and 11 students (15-16 years old) in South Australia enrolled in the trial. A total of 30 522 year 10-12 students received at least 1 dose of 4CMenB. The number of serogroup B IMD cases in 16- to 19-year old adolescents in South Australia increased on average by 10% per year from 2003 to 2016 (95% confidence interval [CI], 6%-15%, P < .001), peaking with 10 cases in 2015. Serogroup B IMD cases reduced to 5 in 2017-2018 and 1 in 2018-2019, below the expected numbers of 9.9 (95% prediction interval [PI], 3.9-17.5) and 10.9 (95% PI, 4.4-19.1), respectively. This translated to an overall reduction in the number of serogroup B IMD cases of 71% (95% CI, 15%-90%, P = .02). There were no serogroup B IMD cases in vaccinated adolescents. Vaccinating adolescents with 4CMenB was associated with a reduction in group B meningococcal disease in South Australia. NCT03089086.

Longitudinal study of meningococcal carriage rates in university entrants living in a dormitory in South Korea.

University students, especially those living in dormitories, are known to have a high risk of invasive meningococcal disease. We performed a longitudinal study to investigate the change in Neisseria meningitidis carriage rates and identify the risk factors for carriage acquisition in university students in South Korea. We recruited university entrants who were admitted to a student dormitory. Pharyngeal swabs were taken from participants at baseline, 1 month, and 3 months, and the subjects completed a questionnaire. Culture and real-time polymerase chain reaction (PCR) for species-specific ctrA and sodC genes were performed. The cultured isolates or PCR-positive samples were further evaluated for epidemiologic characterization using serogrouping, PorA typing, FetA typing, and multilocus sequence typing (MLST). At the first visit, we enrolled 332 participants who were predominantly male (64.2%) with a median age of 19 years. Meningococcal carriage rates increased from 2.7% (95% confidence interval [CI] 0.9–4.4%) at baseline to 6.3% (95% CI 3.4–9.0%) at 1 month and 11.8% (95% CI 7.8–15.6%) at 3 months. Nongroupable isolates accounted for 50.0% of all isolates, with serogroup B being the next most prevalent (24.1%). In the study population, male sex (OR 2.613, 95% CI 1.145–5.961, p = 0.022) and frequent pub or club visits (OR 3.701, 95% CI 1.536–8.919, p = 0.004) were significantly associated with meningococcal carriage. Based on serotype and MLST analyses, six carriers transmitted meningococci to other study participants. N. meningitidis carriage rates among new university entrants who lived in a dormitory significantly increased within the first 3 months of dormitory stay, probably owing to the transmission of identical genotype among students. Based on the risk of meningococcal disease, meningococcal vaccination should be considered for students before dormitory admission.

Carriage of Neisseria meningitidis in Men Who Have Sex With Men Presenting to Public Sexual Health Clinics, New York City.

We conducted a Neisseria meningitidis (Nm) carriage study among men who have sex with men (MSM) to explore possible sexual transmission. We paired information on patient characteristics with oropharyngeal, rectal, and urethral Nm culture results to assess associations with Nm carriage among 706 MSM at New York City sexual health clinics. The Nm isolates were characterized by whole genome sequencing. Twenty-three percent (163 of 706) of MSM were Nm carriers. Oropharyngeal carriage was 22.6% (159 of 703), rectal 0.9% (6 of 695), and urethral 0.4% (3 of 696). Oropharyngeal carriage was associated with the following recent (past 30 days) exposures: 3 or more men kissed (adjusted relative risk [aRR], 1.38; 95% confidence interval [CI], 1.03-1.86), performing oral sex (aRR, 1.81; 95% CI, 1.04-3.18), and antibiotic use (aRR, 0.33; 95% CI, 0.19-0.57). Sixteen clonal complexes were identified; 27% belonged to invasive lineages. Our findings suggest that oral sex and the number of recent kissing partners contribute to Nm carriage in MSM.

Carriage of Neisseria Meningitidis in Low and Middle Income Countries of the Americas and Asia: A Review of the Literature.

IntroductionMeningococcal colonization, or carriage, can progress to invasive meningococcal disease, a serious public health concern, with rapid progression of disease and severe consequences if left untreated. Information on meningococcal carriage and epidemiology in low/middle income American and Asian countries remains sparse. These data are crucial to ensure that appropriate preventive strategies such as vaccination can be implemented in these regions. The goal of this study was to summarize the Neisseria meningitidis carriage literature in low and middle income countries of the Americas and Asia.MethodsTarget countries were categorized as low and middle income according to the International Monetary Fund classification of low income/developing economies and middle income/emerging market economies, respectively. A PubMed search identified English-language publications that examined carriage in these countries. Studies reporting the epidemiology of N. meningitidis carriage or assessing risk factors for carriage were included.ResultsFourteen studies from the Americas [Brazil (n = 7), Chile (n = 3), and Colombia, Cuba, Mexico, and Paraguay (n = 1 each)] and nine from Asia [China (n = 2), India (n = 3), and Malaysia, Nepal, Philippines, and Thailand (n = 1 each)] were identified; an additional Cuban study from the authors’ files was also included. Studies were not identified in many target countries, and substantial diversity was observed among study methodologies, populations, and time periods, thereby limiting comparison between studies. The carriage rate in the Americas ranged from 1.6% to 9.9% and from 1.4% to 14.2% in Asia. Consistent risk factors for carriage were not identified.ConclusionsThere is a lack of comprehensive and contemporary information on meningococcal carriage in low and medium income countries of the Americas and Asia. Future carriage studies should incorporate larger representative populations, a wider age range, and additional countries to improve our understanding of meningococcal epidemiology and disease control.Electronic supplementary materialThe online version of this article (10.1007/s40121-020-00291-9) contains supplementary material, which is available to authorized users.

Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia

BackgroundThe meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain.MethodsWe used cluster randomization to assign, according to school, students in years 10 to 12 (age, 15 to 18 years) in South Australia to receive 4CMenB vaccination either at baseline (intervention) or at 12 months (control). The primary outcome was oropharyngeal carriage of disease-causing Neisseria meningitidis (group A, B, C, W, X, or Y) in students in years 10 and 11, as identified by polymerase-chain-reaction assays for PorA (encoding porin protein A) and N. meningitidis genogroups. Secondary outcomes included carriage prevalence and acquisition of all N. meningitidis and individual disease-causing genogroups. Risk factors for carriage were assessed at baseline.ResultsA total of 237 schools participated. During April through June 2017, a total of 24,269 students in years 10 and 11 and 10,220 students in year 12 were enrolled. At 12 months, there was no difference in the prevalence of carriage of disease-causing N. meningitidis between the vaccination group (2.55%; 326 of 12,746) and the control group (2.52%; 291 of 11,523) (adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.80 to 1.31; P=0.85). There were no significant differences in the secondary carriage outcomes. At baseline, the risk factors for carriage of disease-causing N. meningitidis included later year of schooling (adjusted odds ratio for year 12 vs. year 10, 2.75; 95% CI, 2.03 to 3.73), current upper respiratory tract infection (adjusted odds ratio, 1.35; 95% CI, 1.12 to 1.63), cigarette smoking (adjusted odds ratio, 1.91; 95% CI, 1.29 to 2.83), water-pipe smoking (adjusted odds ratio, 1.82; 95% CI, 1.30 to 2.54), attending pubs or clubs (adjusted odds ratio, 1.54; 95% CI, 1.28 to 1.86), and intimate kissing (adjusted odds ratio, 1.65; 95% CI, 1.33 to 2.05). No vaccine safety concerns were identified.ConclusionsAmong Australian adolescents, the 4CMenB vaccine had no discernible effect on the carriage of disease-causing meningococci, including group B. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT03089086.)

Nasopharyngeal carriage of neisseria meningitidis among medical school students in Turkey.

Objective: Neisseria meningitidis can colonise healthy human nasopharynx and is one of the most important etiologic agent of epidemic meningitis. The purpose of this study is to investigate the carriage rate, serogroup distribution and antibiotic resistance of Neisseria meningitidis in medical faculty students. Methods: Nasopharyngeal swab cultures were evaluated. Identification is made by convensional and semi-otomatised system. Serogroup analysis was performed with slide agglutination method. Minimum inhibitor concentration results were evaluated by gradient test. Risk factors for carriage were investigated. Results: Neisseria meningitidis was isolated from 3 out of 475 (0.6%) students. Two of them were serogroup A and one was serogroup C. All strains were susceptible to penicillin and ceftriaxone. Living in a dormitory and sharing the room with three other students and smoking were found as risk factors. None of the students reported upper respiratory tract infection or antibiotic usage. Other potential pathogenic microorganisms colonising nasopharynx were also identified and most detected of them is methicillin susceptible Staphylococcus aureus (n: 87). Conclusion: Neisseria meningitidis is one of the leading pathogen in our country as it’s in the world. Since serogroups of isolated strains differ from region to region, it’s important that every country should conduct regular surveillance in order to utilize an effective vaccine for prevention and outbreak management against this infection.

Development of a PCR algorithm to detect and characterize Neisseria meningitidis carriage isolates in the African meningitis belt.

Improved methods for the detection and characterization of carried Neisseria meningitidis isolates are needed. We evaluated a multiplex PCR algorithm for the detection of a variety of carriage strains in the meningitis belt. To further improve the sensitivity and specificity of the existing PCR assays, primers for gel-based PCR assays (sodC, H, Z) and primers/probe for real-time quantitative PCR (qPCR) assays (porA, cnl, sodC, H, E, Z) were modified or created using Primer Express software. Optimized multiplex PCR assays were tested on 247 well-characterised carriage isolates from six countries of the African meningitis belt. The PCR algorithm developed enabled the detection of N. meningitidis species using gel-based and real-time multiplex PCR targeting porA, sodC, cnl and characterization of capsule genes through sequential multiplex PCR assays for genogroups (A, W, X, then B, C, Y and finally H, E and Z). Targeting both porA and sodC genes together allowed the detection of meningococci with a sensitivity of 96% and 89% and a specificity of 78% and 67%, for qPCR and gel-based PCR respectively. The sensitivity and specificity ranges for capsular genogrouping of N. meningitidis are 67% - 100% and 98%-100% respectively for gel-based PCR and 90%-100% and 99%-100% for qPCR. We developed a PCR algorithm that allows simple, rapid and systematic detection and characterisation of most major and minor N. meningitidis capsular groups, including uncommon capsular groups (H, E, Z).

Neisseria meningitidis carriage in Swedish teenagers associated with the serogroup W outbreak at the World Scout Jamboree, Japan 2015.

The aims of the study were to estimate the carrier state of Neisseria meningitidis in Swedish teenagers and its association with an outbreak at the World Scout Jamboree in 2015 as well as to compare sensitivity of throat versus nasopharyngeal swab for optimal detection of carriage. In total, 1 705 samples (cultures n = 32, throat swabs n = 715, nasopharyngeal swabs n = 958) from 1 020 Jamboree participants were collected and sent to the National Reference Laboratory for Neisseria meningitidis for culture and molecular analysis. The overall positivity for N. meningitidis was 8% (83/1 020), whereas 2% (n = 22) belonged to a known sero/genogroup while the majority (n = 61) were non-groupable. Throat sample is clearly the sampling method of choice, in 56 individuals where both throat and nasopharynx samples were taken, N. meningitidis was detected in both throat and nasopharynx in eight individuals, in 46 individuals N. meningitidis was only detected in the throat and in two individuals only in the nasopharynx. Carriage studies are important to provide knowledge of the current epidemiology and association between carrier isolates and disease-causing isolates in a given population. Therefore, planning for a carriage study in Sweden is in progress.

A cross-sectional study assessing the pharyngeal carriage of Neisseria meningitidis in subjects aged 1–24 years in the city of Embu das Artes, São Paulo, Brazil

Meningococcal carriage is a prerequisite for invasive infection. This cross-sectional study assessed the pharyngeal carriage prevalence in healthy subjects aged 1–24 years in Embu das Artes city, São Paulo, Brazil. Pharyngeal swabs were examined for the presence of Neisseria meningitidis. The isolates were tested for different serogroups using agglutination and polymerase chain reaction. A logistic regression model assessed any independent association between Neisseria meningitidis carriage and various risk factors. A total of 87/967 subjects (9%, 95% Confidence Interval (CI): 7.3–11.0) tested positive for N. meningitidis: 6.2% (95% CI: 3.8–9.4) in 1–4 years, 8.5% (95% CI: 5.1–13.0) in 5–9 years, 12.5% (95% CI: 7.8–18.6) in 10–14 years, 12.6% (95% CI: 7.4–19.7) in 15–19 years and 9% (95% CI: 4.9–14.9) in 20–24 years age groups. Highest carriage prevalence was observed in adolescents 10–19 years old. Serogroup C was predominant (18.4%) followed by serogroup B (12.6%). The 15–19 years age group showed a significant association between number of household members and carriers of N. meningitidis. This cross-sectional study is the first in Brazil to evaluate meningococcal carriage prevalence and associated factors in a wide age range.

Molecular Characteristics of Neisseria Meningitidis Carriage Strains Isolated from Korean Adolescents

Molecular Characteristics of Neisseria Meningitidis Carriage Strains Isolated from Korean Adolescents

Optimization of Molecular Approaches to Genogroup Neisseria meningitidis Carriage Isolates and Implications for Monitoring the Impact of New Serogroup B Vaccines.

The reservoir for Neisseria meningitidis (Nm) is the human oropharynx. Implementation of Nm serogroup C (NmC) glycoconjugate vaccines directly reduced NmC carriage. Prophylactic vaccines are now available to prevent disease caused by the five major Nm disease causing serogroups (ABCWY). Nm serogroup B (NmB) vaccines are composed of antigens that are conserved across Nm serogroups and therefore have the potential to impact all Nm carriage. To assess the effect of these vaccines on carriage, standardized approaches to identify and group Nm are required. Real-time PCR (rt-PCR) capsule grouping assays that were internally controlled to confirm Nm species were developed for eight serogroups associated with carriage (A, B, C, E, W, X, Y and Z). The grouping scheme was validated using diverse bacterial species associated with carriage and then used to evaluate a collection of diverse Nm carriage isolates (n=234). A scheme that also included porA and ctrA probes was able to speciate the isolates, while ctrA also provided insights on the integrity of the polysaccharide loci. Isolates were typed for the Nm vaccine antigen factor H binding protein (fHbp), and were found to represent the known diversity of this antigen. The porA rt-PCR yielded positive results with all 234 of the Nm carriage isolates. Genogrouping assays classified 76.5% (179/234) of these isolates to a group, categorized 53 as nongenogroupable (NGG) and two as mixed results. Thirty seven NGG isolates evidenced a disrupted capsular polysaccharide operon judged by a ctrA negative result. Only 28.6% (67/234) of the isolates were serogrouped by slide agglutination (SASG), highlighting the reduced capability of carriage strains to express capsular polysaccharide. These rt-PCR assays provide a comprehensive means to identify and genogroup N. meningitidis in carriage studies used to guide vaccination strategies and to assess the impact of novel fHbp containing vaccines on meningococcal carriage.

Nasal Inoculation of the Commensal Neisseria lactamica Inhibits Carriage of Neisseria meningitidis by Young Adults: A Controlled Human Infection Study.

Herd protection by meningococcal vaccines is conferred by population-level reduction of meningococcal nasopharyngeal colonization. Given the inverse epidemiological association between colonization by commensal Neisseria lactamica and meningococcal disease, we investigated whether controlled infection of human volunteers with N. lactamica prevents colonization by Neisseria meningitidis. In a block-randomized human challenge study, 310 university students were inoculated with 10(4) colony-forming units of N. lactamica or were sham-inoculated, and carriage was monitored for 26 weeks, after which all participants were reinoculated with N. lactamica and resampled 2 weeks later. At baseline, natural N. meningitidis carriage in the control group was 22.4% (36/161), which increased to 33.6% (48/143) by week 26. Two weeks after inoculation of N. lactamica, 33.6% (48/143) of the challenge group became colonized with N. lactamica. In this group, meningococcal carriage reduced from 24.2% (36/149) at inoculation to 14.7% (21/143) 2 weeks after inoculation (-9.5%; P = .006). The inhibition of meningococcal carriage was only observed in carriers of N. lactamica, was due both to displacement of existing meningococci and to inhibition of new acquisition, and persisted over at least 16 weeks. Crossover inoculation of controls with N. lactamica replicated the result. Genome sequencing showed that inhibition affected multiple meningococcal sequence types. The inhibition of meningococcal carriage by N. lactamica is even more potent than after glycoconjugate meningococcal vaccination. Neisseria lactamica or its components could be a novel bacterial medicine to suppress meningococcal outbreaks. This observation explains the epidemiological observation of natural immunity conferred by carriage of N. lactamica. NCT02249598.

Sterilizing immunity elicited by Neisseria meningitidis carriage shows broader protection than predicted by serum antibody cross-reactivity in CEACAM1-humanized mice.

Neisseria meningitidis asymptomatically colonizes the human upper respiratory tract but is also the cause of meningitis and severe septicemia. Carriage or disease evokes an immune response against the infecting strain. Hitherto, we have known little about the breadth of immunity induced by natural carriage of a single strain or its implications for subsequent infectious challenge. In this study, we establish that transgenic mice expressing human CEACAM1 support nasal colonization by a variety of strains of different capsular types. Next, we nasally challenged these mice with either of the N. meningitidis strains H44/76 (serogroup B, ST-32) and 90/18311 (serogroup C, ST-11), while following the induction of strain-specific immunoglobulin. When these antisera were tested for reactivity with a diverse panel of N. meningitidis strains, very low levels of antibody were detected against all meningococcal strains, yet a mutually exclusive "fingerprint" of high-level cross-reactivity toward certain strains became apparent. To test the efficacy of these responses for protection against subsequent challenge, CEACAM1-humanized mice exposed to strain 90/18311 were then rechallenged with different N. meningitidis strains. As expected, the mice were immune to challenge with the same strain and with a closely related ST-11 strain, 38VI, while H44/76 (ST-32) could still colonize these animals. Notably, however, despite the paucity of detectable humoral response against strain 196/87 (ST-32), this strain was unable to colonize the 90/18311-exposed mice. Combined, our data suggest that current approaches may underestimate the actual breadth of mucosal protection gained through natural exposure to N. meningitidis strains.

Potential impact of the bivalent rLP2086 vaccine on Neisseria meningitidis carriage and invasive serogroup B disease

Asymptomatic throat carriage of Neisseria meningitidis is common in healthy individuals. In unusual cases, the bacteria become invasive, resulting in life-threatening disease. Effective meningococcal serogroup B (MnB) vaccines should provide broad protection against disease-causing strains and may confer indirect protection by impacting carriage and subsequent transmission. Factor H binding proteins (fHBPs), components of MnB vaccines in development, are classified into two immunologically distinct subfamilies (A and B). fHBP variants of MnB strains carried by adolescents are similar to those detected in infants with MnB disease. A vaccine containing subfamily A and B fHBP variants elicited bactericidal antibody responses (titers ≥ 1:4) against MnB strains expressing fHBP variants common to carriage strains and strains that cause disease in adolescents and infants in 75–100% of adolescent study subjects. This suggests that the bivalent fHBP vaccine has the potential to provide protection against invasive MnB strains and interrupt meningococcal carriage, which may also reduce infant MnB disease.