Cases of Meningococcal Disease Associated with Travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).

Antibody persistence and revaccination recommendations of MenACWY-TT: a review of clinical studies assessing antibody persistence up to 10 years after vaccination.

INTRODUCTION: Invasive meningococcal disease (IMD) is potentially fatal and associated with severe sequelae among survivors. It is preventable by several vaccines, including meningococcal vaccines targeting the most common disease-causing serogroups (A, B, C, W, Y). The meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT [Nimenrix]) is indicated from 6 weeks of age in the European Union and >50 additional countries. AREAS COVERED: Using PubMed, Google Scholar, ClinicalTrials.gov and ad hoc searches for publications to June 2023, we review evidence of antibody persistence for up to 10 years after primary vaccination and up to 6 years after MenACWY-TT revaccination. We also review global MenACWY revaccination recommendations and real-world impact of vaccination policies, focusing on how these data can be considered alongside antibody persistence data to inform future IMD prevention strategies. EXPERT OPINION: Based on clear evidence that immunogenicity data (demonstrated antibody titers above established correlates of protection) are correlated with real-world effectiveness, long-term persistence of antibodies after MenACWY-TT vaccination suggests continuing protection against IMD. Optimal timing of primary and subsequent vaccinations is critical to maximize direct and indirect protection. Recommending bodies should carefully consider factors such as age at vaccination and long-term immune responses associated with the specific vaccine being used.

Prediction by genetic MATS of 4CMenB vaccine strain coverage of invasive meningococcal serogroup B isolates circulating in Taiwan between 2003 and 2020.

Neisseria meningitidis serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic Meningococcal Antigen Typing System (gMATS), a correlate of MATS estimates, predicts strain coverage by the 4-component MenB (4CMenB) vaccine in cultivable and non-cultivable NmB isolates. In Taiwan, 134 invasive, disease-causing NmB isolates were collected in 2003-2020 (23.1%, 4.5%, 5.2%, 29.8%, and 37.3% from individuals aged ≤11 months, 12-23 months, 2-4 years, 5-29 years, and ≥30 years, respectively). NmB isolates were characterized by whole-genome sequencing and vaccine antigen genotyping, and 4CMenB strain coverage was predicted using gMATS. Analysis of phylogenetic relationships with 502 global NmB genomes showed that most isolates belonged to three global hyperinvasive clonal complexes: ST-4821 (27.6%), ST-32 (23.9%), and ST-41/44 (14.9%). Predicted strain coverage by gMATS was 62.7%, with 27.6% isolates covered, 2.2% not covered, and 66.4% unpredictable by gMATS. Age group coverage point estimates ranged from 42.9% (2-4 years) to 66.1% (≤11 months). Antigen coverage estimates and percentages predicted as covered/not covered were highly variable, with higher estimates for isolates with one or more gMATS-positive antigens than for isolates positive for one 4CMenB antigen. In conclusion, this first study on NmB strain coverage by 4CMenB in Taiwan shows 62.7% coverage by gMATS, with predictable coverage for 29.8% of isolates. These could be underestimated since the gMATS calculation does not consider synergistic mechanisms associated with simultaneous antibody binding to multiple targets elicited by multicomponent vaccines or the contributions of minor outer membrane vesicle vaccine components.IMPORTANCEMeningococcal diseases, caused by the bacterium Neisseria meningitidis (meningococcus), include meningitis and septicemia. Although rare, invasive meningococcal disease is often severe and can be fatal. Nearly all cases are caused by six meningococcal serogroups (types), including meningococcal serogroup B. Vaccines are available against meningococcal serogroup B, but the antigens targeted by these vaccines have highly variable genetic features and expression levels, so the effectiveness of vaccination may vary depending on the strains circulating in particular countries. It is therefore important to test meningococcal serogroup B strains isolated from specific populations to estimate the percentage of bacterial strains that a vaccine can protect against (vaccine strain coverage). Meningococcal isolates were collected in Taiwan between 2003 and 2020, of which 134 were identified as serogroup B. We did further investigations on these isolates, including using a method (called gMATS) to predict vaccine strain coverage by the 4-component meningococcal serogroup B vaccine (4CMenB).

Children with perinatally acquired HIV exhibit distinct immune responses to 4CMenB vaccine.

Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy-treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.

Hybrid response to SARS-CoV-2 and Neisseria meningitidis C after an OMV-adjuvanted immunization in mice and their offspring.

COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 µg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.

Mpox in children and adolescents and contact follow-up in school settings in greater Paris, France, May 2022 to July 2023.

BackgroundDuring the 2022 mpox outbreak in Europe, primarily affecting men who have sex with men, a limited number of cases among children and adolescents were identified. Paediatric cases from outbreaks in endemic countries have been associated with a higher likelihood of severe illness. Detailed clinical case descriptions and interventions in school settings before 2022 are limited.AimTo describe clinical characteristics of mpox cases among children (< 15 years) and adolescents (15-17 years) in the greater Paris area in France, and infection control measures in schools.MethodsWe describe all notified laboratory-confirmed and non-laboratory-confirmed cases among children and adolescents identified from May 2022 to July 2023, including demographic and clinical characterisation and infection control measures in school settings, i.e. contact tracing, contact vaccination, secondary attack rate and post-exposure vaccination uptake.ResultsNineteen cases were notified (13 children, 6 adolescents). Four adolescent cases reported sexual contact before symptom onset. Ten child cases were secondary cases of adult patients; three cases were cryptic, with vesicles on hands, arms and/or legs and one case additionally presented with genitoanal lesions. Five cases attended school during their infectious period, with 160 at-risk contacts identified, and one secondary case. Five at-risk contacts were vaccinated following exposure.ConclusionCases among children and adolescents are infrequent but require a careful approach to identify the source of infection and ensure infection control measures. We advocate a 'contact warning' strategy vs 'contact tracing' in order to prevent alarm and stigma. Low post-exposure vaccination rates are expected.

Use of the Pfizer Pentavalent Meningococcal Vaccine Among Persons Aged ≥10 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.

Analyzing the dynamics of meningococcal vaccinations initiatives by local government units in Poland (2017-2021) - Scope, challenges and recommendations.

INTRODUCTION: Meningococcal vaccinations are recommended by Polish public health authorities but lack coverage under health insurance, prompting Local Government Units (LGUs) to implement local health policy programs. This study examines the effectiveness and impact of LGU-driven meningococcal vaccination initiatives in Poland between 2017 and 2021. MATERIAL AND METHODS: A retrospective analysis utilized data from reports on local public health interventions submitted annually to the Ministry of Health in Poland. The study focused on the number of meningococcal vaccination programs, their scope, the vaccinated population, and associated program costs. Additionally, nationwide data on meningococcal disease incidence and vaccine uptake were analyzed. RESULTS: Within LGUs programs, 48,617 individuals received meningococcal vaccinations, constituting approximately 10% of all vaccinations in Poland during the study period. Notably, cities with poviat rights spearheaded programs covering 54% of the total participants. The total cost incurred by these initiatives amounted to EUR 2,553,661. CONCLUSIONS: While LGUs activities positively contributed to increased meningococcal vaccination rates, the overall engagement of local governments remains limited. The findings underscore the importance of expanding local government involvement in meningococcal vaccination programs to address public health needs effectively. Improved collaboration and increased funding may enhance the reach and impact of these initiatives.

Available evidence on the co-administration of the four-component meningococcal B vaccine (4CMenB) with three vaccines at the same visit among pediatric individuals.

Vaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023 included recommendations for co-administration of pediatric vaccines, including the four-component vaccine for meningococcus B (4CMenB), pneumococcal conjugate vaccine (PCV), hexavalent vaccines, and oral rotavirus vaccines. Safety is a major concern when considering vaccine co-administration; therefore, a literature review of the available evidence on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines was performed. Of 763 publications screened, two studies were reviewed that reported safety data on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines in infants aged 0-24 months. Overall, these studies supported that there were no significant safety signals when co-administering 4CMenB with PCV, hexavalent/pentavalent, and rotavirus vaccines, compared with individual vaccination. This review provides key insights for healthcare professionals on the tolerability of co-administering 4CMenB with routine vaccines.

Meningococcal Vaccination of Adolescents in the United States: Past Successes and Future Considerations.

Invasive meningococcal disease (IMD) is a rare but serious illness, and adolescents and young adults in the United States are at increased risk. Here, we discuss US IMD history and how successful disease prevention through routine vaccination against the most common disease-causing serogroups (A, B, C, W, and Y) can inform future recommendations. Before the introduction of quadrivalent meningococcal conjugate (MenACWY) vaccines, most US cases of IMD were caused by serogroups B, C, and Y. After recommendation by the Advisory Committee on Immunization Practices for routine MenACWY vaccination of 11-12-year-olds in 2005, followed by a 2010 booster recommendation, MenCWY disease incidence declined dramatically, and vaccine coverage remains high. Two serogroup B (MenB) vaccines are licensed in the United States, but uptake is low compared with MenACWY vaccines, likely because Advisory Committee on Immunization Practices recommends MenB vaccination subject to shared clinical decision-making rather than routinely for all adolescents. The proportion of adolescent IMD caused by MenB has now increased. Pentavalent vaccines that protect against serogroups A, B, C, W, and Y may provide an optimal strategy for improving vaccination rates to ultimately reduce MenB incidence while maintaining the historically low rates of IMD caused by serogroups A, C, W, and Y.

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.

The important lessons lurking in the history of meningococcal epidemiology.

INTRODUCTION: The epidemiology of invasive meningococcal disease (IMD), a rare but potentially fatal illness, is typically described as unpredictable and subject to sporadic outbreaks. AREAS COVERED: Meningococcal epidemiology and vaccine use during the last ~ 200 years are examined within the context of meningococcal characterization and classification to guide future IMD prevention efforts. EXPERT OPINION: Historical and contemporary data highlight the dynamic nature of meningococcal epidemiology, with continued emergence of hyperinvasive clones and affected regions. Recent shifts include global increases in serogroup W disease, meningococcal antimicrobial resistance (AMR), and meningococcal urethritis; additionally, unvaccinated populations have experienced disease resurgences following lifting of COVID-19 restrictions. Despite these changes, a close analysis of meningococcal epidemiology indicates consistent dominance of serogroups A, B, C, W, and Y and elevated IMD rates among infants and young children, adolescents/young adults, and older adults. Demonstrably effective vaccines against all 5 major disease-causing serogroups are available, and their prophylactic use represents a powerful weapon against IMD, including AMR. The World Health Organization's goal of defeating meningitis by the year 2030 demands broad protection against IMD, which in turn indicates an urgent need to expand meningococcal vaccination programs across major disease-causing serogroups and age-related risk groups.

United States Physicians' Knowledge, Attitudes, and Practices Regarding Meningococcal Vaccination for Healthy Adolescents and Young Adults.

PURPOSE: The United States Advisory Committee on Immunization Practices (ACIP) recommends vaccination against meningococcal serogroups A, C, W, and Y (MenACWY) for all 11-12-year-olds, with a booster dose for 16-year-olds, and against meningococcal serogroup B (MenB) for 16-23-year-olds under shared clinical decision-making (SCDM). However, uptake of the MenB vaccine and the MenACWY booster dose is low. This study investigated United States physicians' knowledge, attitudes, and practices regarding recommending MenB and MenACWY vaccines to non-high-risk older adolescents and young adults. METHODS: An online survey was conducted in April-May 2022 among pediatricians, family physicians (FPs), general practitioners (GPs), and internists who had recommended the MenB and/or the MenACWY vaccine(s) to at least one 16-23-year-old in the past year. RESULTS: Among 407 participants, 50% correctly identified MenB as the leading cause of meningococcal disease among adolescents and young adults. Furthermore, 46% of physicians (47% of pediatricians, 40% of FPs and GPs, 53% of internists) answered correctly that MenB vaccination is recommended under SCDM, and 82% of physicians (96% of pediatricians, 70% of FPs and GPs, 65% of internists) answered correctly that MenACWY vaccination is routinely recommended. Among MenB-vaccinators, 78% reported having received some training or other information on implementing SCDM, and 65% rated recommending MenB vaccination as very important. DISCUSSION: Knowledge gaps, which varied by specialty, were identified regarding meningococcal disease and vaccine recommendations, particularly regarding MenB. Targeted education of physicians may facilitate discussions about MenB vaccination.

From Qualitative Research to Quantitative Preference Elicitation: An Example in Invasive Meningococcal Disease.

BACKGROUND: Qualitative research is fundamental for designing discrete choice experiments (DCEs) but is often underreported in the preference literature. We developed a DCE to elicit preferences for vaccination against invasive meningococcal disease (IMD) among adolescents and young people (AYP) and parents and legal guardians (PLG) in the United States. This article reports the targeted literature review and qualitative interviews that informed the DCE design and demonstrates how to apply the recent reporting guidelines for qualitative developmental work in preference studies. METHODS: This study included two parts: a targeted literature review and qualitative interviews. The Medline and Embase databases were searched for quantitative and qualitative studies on IMD and immunization. The results of the targeted literature review informed a qualitative interview guide. Sixty-minute, online, semi-structured interviews with AYP and PLG were used to identify themes related to willingness to be vaccinated against IMD. Participants were recruited through a third-party recruiter's database and commercial online panels. Interviews included vignettes about IMD and vaccinations and three thresholding exercises examining the effect of incidence rate, disability rate, and fatality rate on vaccination preferences. Participant responses related to the themes were counted. RESULTS: The targeted literature review identified 31 concepts that were synthesized into six topics for the qualitative interviews. Twenty AYP aged 16-23 years and 20 PLG of adolescents aged 11-17 years were interviewed. Four themes related to willingness to be vaccinated emerged: attitudes towards vaccination, knowledge and information, perception of IMD, and vaccine attributes. Most participants were concerned about IMD (AYP 60%; PLG 85%) and had positive views of vaccination (AYP 80%; PLG 60%). Ninety percent of AYP and 75% of PLG always chose vaccination over no vaccination, independent of IMD incidence rate, disability rate, or fatality rate. CONCLUSION: Willingness to be vaccinated against IMD was affected by vaccine attributes but largely insensitive to IMD incidence and severity. This article provides an example of how to apply the recent reporting guidelines for qualitative developmental work in preference studies, with 21 out of 22 items in the guidelines being considered.

Epitope Mapping of Human Polyclonal Antibodies to the fHbp Antigen of a Neisseria Meningitidis Vaccine by Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS).

Antigen-antibody interactions play a key role in the immune response post vaccination and the mechanism of action of antibody-based biopharmaceuticals. 4CMenB is a multicomponent vaccine against Neisseria meningitidis serogroup B in which factor H binding protein (fHbp) is one of the key antigens. In this study, we use hydrogen/deuterium exchange mass spectrometry (HDX-MS) to identify epitopes in fHbp recognized by polyclonal antibodies (pAb) from two human donors (HDs) vaccinated with 4CMenB. Our HDX-MS data reveal several epitopes recognized by the complex mixture of human pAb. Furthermore, we show that the pAb from the two HDs recognize the same epitope regions. Epitope mapping of total pAb and purified fHbp-specific pAb from the same HD reveals that the two antibody samples recognize the same main epitopes, showing that HDX-MS based epitope mapping can, in this case at least, be performed directly using total IgG pAb samples that have not undergone Ab-selective purification. Two monoclonal antibodies (mAb) were previously produced from B-cell repertoire sequences from one of the HDs and used for epitope mapping of fHbp with HDX-MS. The epitopes identified for the pAb from the same HD in this study, overlap with the epitopes recognized by the two individual mAbs. Overall, HDX-MS epitope mapping appears highly suitable for simultaneous identification of epitopes recognized by pAb from human donors and to thus both guide vaccine development and study basic human immunity to pathogens, including viruses.

Selection of Antibiotics as Prophylaxis for Close Contacts of Patients with Meningococcal Disease in Areas with Ciprofloxacin Resistance - United States, 2024.

Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a rare but life-threatening illness that requires prompt antibiotic treatment for patients and antibiotic prophylaxis for their close contacts. Historically, N. meningitidis isolates in the United States have been largely susceptible to the antibiotics recommended for prophylaxis, including ciprofloxacin. Since 2019, however, the number of meningococcal disease cases caused by ciprofloxacin-resistant strains has increased. Antibiotic prophylaxis with ciprofloxacin in areas with ciprofloxacin resistance might result in prophylaxis failure. Health departments should preferentially consider using antibiotics other than ciprofloxacin as prophylaxis for close contacts when both of the following criteria have been met in a local catchment area during a rolling 12-month period: 1) the reporting of two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains, and 2) ≥20% of all reported invasive meningococcal disease cases are caused by ciprofloxacin-resistant strains. Other than ciprofloxacin, alternative recommended antibiotic options include rifampin, ceftriaxone, or azithromycin. Ongoing monitoring for antibiotic resistance of meningococcal isolates through surveillance and health care providers' reporting of prophylaxis failures will guide future updates to prophylaxis considerations and recommendations.