Woo-Yun Sohn

Individuals with immunocompromising conditions (e.g. asplenia, complement deficiency, HIV infection) or with high exposure to Neisseria meningitidis (e.g. laboratory workers, those in outbreak settings) have an increased risk of meningococcal disease. Immunization with meningococcal serogroups ACWY (MenACWY) and serogroup B (MenB) vaccines is recommended for high-risk groups in many countries, although definitions of high-risk vary. There are not yet clinical data for the pentavalent meningococcal serogroups ABCWY (MenABCWY) vaccines in high-risk populations. This review examines studies conducted in high-risk groups with the component vaccines of GSK's MenABCWY vaccine, the 4-component MenB vaccine (4CMenB) and quadrivalent MenACWY CRM₁₉₇-glycoconjugate vaccine (MenACWY-CRM). These component vaccines have been licensed for more than 10 years and are recommended in groups categorized as high risk. The component vaccines of GSK's MenABCWY vaccine, 4CMenB and MenACWY-CRM, have demonstrated immunogenicity and safety in high-risk groups, including with concomitant or sequential vaccine administration. As expected, immunogenicity was reduced in patients with complement deficiencies, particularly those receiving eculizumab. Further data are required on meningococcal vaccination in high-risk groups for the future refinement of national and regional recommendations and to support proactive approaches to improve vaccine uptake in high-risk groups.

Meningococcal serogroup B (MenB) vaccine licensure was based on the assessment of vaccine-induced immune responses by human serum bactericidal antibody (hSBA) assay against a small number of antigen-specific strains complemented by strain coverage predictions. However, the evaluation of vaccine strain coverage is challenging because of genotypic and phenotypic diversity in surface-exposed MenB strain antigens. This narrative review considers the principal methods applied to assess the performance of a multicomponent MenB vaccine at different stages of its development. Traditional hSBA assay against a limited panel of strains is useful at all stages, while predicted strain coverage methods, such as the meningococcal antigen typing system, are used independent of clinical trials. A new method, the endogenous complement hSBA assay, has been developed to evaluate a vaccine’s ability to induce a bactericidal immune response in clinical trials, in conditions that approximate real-world settings through the use of each vaccinee’s serum as a source of complement and by testing against a panel of 110 epidemiologically representative MenB strains. Each assay, therefore, has a different scope during the vaccine’s development and all complement each other, enabling comprehensive evaluation of the performance of multicomponent MenB vaccines, in advance of real-world evidence of vaccine effectiveness and vaccine impact.

Purpose: To describe the relationships between Neisseria meningitidis (NM) and Neisseria gonorrhoeae (NG) at genetic, population, and individual levels; to review historical trends in antimicrobial resistance (AMR); to review the treatment and preventive landscapes and explore their potential impact on AMR. Methods: A narrative literature search was conducted in PubMed, with searches restricted to 2003–2023 and additional articles included based on expertise. Results: NM and NG are closely related bacterial pathogens causing invasive meningococcal disease (IMD) and gonorrhea, respectively. NM can currently be treated with most antibiotics and generally has a wild-type susceptibility profile, whereas NG is increasingly resistant even in the first line of treatment. These pathogens share 80–90% genetic identity and can asymptomatically cohabit the pharynx. While AMR has historically been rare for NM, recent reports show this to be an emerging clinical concern. Extensively drug-resistant NG are reported globally, with data available from 73 countries, and can lead to treatment failure. Importantly, Neisseria commensals within the normal microbiota in the pharynx can act as a genetic reservoir of resistance to extended-spectrum cephalosporins. Novel oral antibiotics are urgently needed to treat a growing threat from antibiotic-resistant NG, recognized as a major global concern to public health by the World Health Organization. Numerous vaccines are available to prevent IMD, but none are approved for gonorrhea. Research to identify suitable candidates is ongoing. Conclusion: Holistic management of AMR in IMD and gonorrhea should couple judicious use of existing antibiotics, optimization of vaccination programs, and development of novel antibiotics and vaccines. Graphical

Background Invasive meningococcal disease (IMD) is primarily associated with five Neisseria meningitidis serogroups: A, B, C, W, or Y. In the United States (US), available vaccines protect against serogroups B (MenB), A, C, W, and Y (MenACWY), and A, B, C, W, and Y (MenABCWY). The Advisory Committee on Immunization Practices is re-evaluating the adolescent meningococcal vaccination schedule with varying recommendation formats. This analysis aimed to predict which schedule could avert the most IMD cases and have the most positive public health impact (PHI). Methods An epidemiological model compared the 15-year PHI of vaccination schedules using MenB, MenACWY, and/or MenABCWY vaccines versus current US standard of care (SoC). Varying coverage rates reflected routine, shared clinical decision making, and risk-based recommendations. Sensitivity analyses assessed robustness of the results to different inputs/assumptions. Results The most positive PHI compared with SoC was observed with one dose of MenACWY at 11 years of age and two doses of MenABCWY (6 months apart) at 16 years of age, assuming routine recommendation and coverage reflecting real-world uptake of MenACWY. This strategy resulted in 123 IMD cases averted (MenB: 59, MenACWY: 64), 17 deaths prevented, 574 life-years saved, and 757 quality-adjusted life-years gained versus SoC. Eliminating MenACWY vaccination at 11 years was found to result in an additional IMD burden. Conclusion A routinely recommended two-dose pentavalent vaccine, with doses administered 6 months apart at 16 years of age, alongside the routinely recommended MenACWY vaccine at 11 years of age, would improve the PHI and benefits of IMD vaccination to society. Graphical Abstract

In 2005, the United States Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination against invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y (MenACWY) for all 11-12-year-olds, as well as 2-10-year-olds at high risk. In 2010, a booster dose was recommended for all 16-year-olds, as well as for high-risk patients every 3-5 years. In 2015, optional (as opposed to routine) vaccination against meningococcal serogroup B (MenB) at the preferred age of 16-18 years was recommended (Category B, later changed to shared clinical decision-making). In 2023, a vaccine (MenABCWY) against the 5 serogroups primarily responsible for IMD in the US became available. This review summarizes the evolution of public policy that led to each milestone vaccine recommendation, reviews epidemiologic data published following the recommendations, and discusses the current state of meningococcal immunization policy. The use of MenABCWY has the potential to consolidate policy, improve coverage rates for the 5 serogroups, address disparities in vaccination coverage, and simplify vaccine delivery.

Several observational studies showed the added gonorrhea protection of outer membrane vesicle (OMV)-containing meningococcal B (MenB) vaccines, raising hopes for achieving WHO gonorrhea control targets. With evolving meningococcal vaccine recommendations in the United States (US), a key policy consideration can be the optimal age for adolescent MenB immunization considering added gonorrhea protection. This study assessed the additional gonorrhea public health impact that could be achieved in the two major existing meningococcal vaccination platforms at 11 and 16-18 years of age in the US. Even with low coverage and without considering disease transmission, an OMV-containing MenB vaccine recommendation for older adolescents could result in significantly higher gonorrhea public health impact compared to younger adolescents. Dual effects for MenB and gonorrhea could be considered when recommending vaccines based on age of vaccination. Zeki Kocaata, PhD, GSK: Stocks/Bonds Menaka Bhor, PhD, GSK: Stocks/Bonds Woo-Yun Sohn, MD, GSK: Stocks/Bonds Kinga Meszaros, MBA, GSK: Employee|GSK: Stocks/Bonds

The four-component meningococcal serogroup B vaccine (4CMenB) is indicated for the prevention of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B. Co-administering 4CMenB with other vaccines may improve vaccine uptake provided that the safety and immunogenicity of either are not affected. Published literature on the immunogenicity and reactogenicity of 4CMenB co-administered with other routine childhood and adulthood vaccines was reviewed. From 282 publications identified, data were collated from 10 clinical studies, 3 real-world studies, and 3 reviews. The evidence showed that 4CMenB co-administration is not associated with significant safety concerns or clinically relevant immunological interferences. The increased reactogenicity (e.g., fever) associated with 4CMenB co-administration can be adequately managed with prophylactic paracetamol in children. Thus, 4CMenB co-administration has the potential to maximize vaccine coverage and improve protection against IMD globally.

Neisseria meningitidis serogroup B (NmB) antigens are inherently diverse with variable expression among strains. Prediction of meningococcal B (MenB) vaccine effectiveness therefore requires an assay suitable for use against large panels of epidemiologically representative disease-causing NmB strains. Traditional serum bactericidal antibody assay using exogenous human complement (hSBA) is limited to the quantification of MenB vaccine immunogenicity on a small number of indicator strains. Additional and complementary methods for assessing strain coverage developed previously include the Meningococcal Antigen Typing System (MATS), Meningococcal Antigen Surface Expression (MEASURE) assay, and genotyping approaches, but these do not estimate vaccine effectiveness. We provide a narrative review of these methods, highlighting a more recent approach involving the hSBA assay in conjunction with expanded NmB strain panels: hSBA assay using endogenous complement in each vaccinated person's serum (enc-hSBA) against a 110-strain NmB panel and the traditional hSBA assay against 14 (4 + 10) NmB strains. The enc-hSBA is a highly standardized, robust method that can be used in clinical trials to measure the immunological effectiveness of MenB vaccines under conditions that mimic real-world settings as closely as possible, through the use of endogenous complement and a diverse, epidemiologically representative panel of NmB strains.

Background: The benefits of preventive interventions lack comprehensive evaluation in standard health technology assessments (HTA), particularly for rare and transmissible diseases.

Invasive meningococcal disease is a life-threatening infection preventable through vaccination. Pediatric vaccination rates have declined during the coronavirus disease 2019 (COVID-19) pandemic. This survey aimed to understand how parents’ attitudes and behaviors have changed during the pandemic with regard to immunization and, more specifically, meningococcal vaccination. An online survey was emailed to parents of eligible children 0–4 years, following the selection process from UK, France, Germany, Italy, Brazil, Argentina, and Australia; and of adolescents 11–18 years from US. Data collection took place 19 January–16 February 2021. Quotas were set to ensure a representative sample. Eleven questions relating to general perceptions around vaccination and attitudes and behaviors toward meningitis vaccination were displayed. On 4,962 parents (average 35 years) participating in the survey, most (83%) believed important for their child to continue receiving recommended vaccines during the COVID-19 pandemic. Nearly half of routine vaccine appointments were delayed or canceled due to the pandemic, and 61% of respondents were likely to have their children catch up once COVID-19 restrictions were lifted. 30% of meningitidis vaccination appointments were canceled or delayed during the pandemic, and 21% of parents did not intend to reschedule them because of lockdown/stay at home regulations, and fear of catching COVID-19 in public places. It is crucial to communicate clear instructions to health workers and the general population and to provide appropriate safety precautions in vaccination centers. This will help to maintain vaccination rates and limit infections to prevent future outbreaks. What is the context? What is new? What is the impact?