Epidemiology of invasive meningococcal disease worldwide from 2010-2019: a literature review.

The epidemiology of invasive meningococcal disease (IMD) is unpredictable, varies by region and age group and continuously evolves. This review aimed to describe trends in the incidence of IMD and serogroup distribution by age group and global region over time. Data were extracted from 90 subnational, national and multinational grey literature surveillance reports and 22 published articles related to the burden of IMD from 2010 to 2019 in 77 countries. The global incidence of IMD was generally low, with substantial variability between regions in circulating disease-causing serogroups. The highest incidence was usually observed in infants, generally followed by young children and adolescents/young adults, as well as older adults in some countries. Globally, serogroup B was a predominant cause of IMD in most countries. Additionally, there was a notable increase in the number of IMD cases caused by serogroups W and Y from 2010 to 2019 in several regions, highlighting the unpredictable and dynamic nature of the disease. Overall, serogroups A, B, C, W and Y were responsible for the vast majority of IMD cases, despite the availability of vaccines to prevent disease due to these serogroups.

Evolution of invasive meningococcal disease epidemiology in Europe, 2008 to 2017.

BackgroundInvasive meningococcal disease (IMD) epidemiology has fluctuated over the past 25 years and varies among serogroups, age groups and geographical locations.AimThis study analysed the evolution of European IMD epidemiology from 2008 to 2017 to identify trends.MethodsReported number of IMD cases and associated incidence were extracted from the European Centre for Disease Prevention and Control Surveillance Atlas for Infectious Diseases for individual European countries. Epidemiology and its evolution were analysed by serogroup and age group.ResultsOverall IMD incidence decreased by 34.4% between 2008 and 2017. Serogroup B remained predominant in 2017; despite a 56.1% decrease over the 10-year period, the rate of decrease has slowed in recent years and varies by age group. Serogroup C was the second most prevalent serogroup until 2016. Its incidence decreased among individuals aged 1-24 years, the main population targeted by MenC vaccination campaigns, but increases have occurred in other age groups. Incidences of serogroups W and Y were low but increased by > 500% and > 130% (to 0.10 and 0.07/100,000) respectively, from 2008 to 2017. Considering all serogroups, a marked modification of the evolution trends by age group has occurred, with increases in incidence mainly affecting older age groups.ConclusionAlthough the overall IMD incidence decreased in Europe between 2008 and 2017, increases were observed for serogroups W and Y, and in the older population when considering all serogroups. It may be necessary to adapt current vaccination strategies to reflect epidemiological changes and their likely future evolution.

Systematic literature review of the impact and effectiveness of monovalent meningococcal C conjugated vaccines when used in routine immunization programs.

BACKGROUND: Monovalent meningococcal C conjugate vaccine (MCCV) was introduced into the routine immunization program in many countries in Europe and worldwide following the emergence of meningococcal serogroup C (MenC) in the late 1990s. This systematic literature review summarizes the immediate and long-term impact and effectiveness of the different MCCV vaccination schedules and strategies employed. METHODS: We conducted a systematic literature search for peer-reviewed, scientific publications in the databases of MEDLINE (via PubMed), LILACS, and SCIELO. We included studies from countries where MCCV have been introduced in routine vaccination programs and studies providing the impact and effectiveness of MCCV published between 1st January 2001 and 31st October 2017. RESULTS: Forty studies were included in the review; 30 studies reporting impact and 17 reporting effectiveness covering 9 countries (UK, Spain, Italy, Canada, Brazil, Australia, Belgium, Germany and the Netherlands). Following MCCV introduction, significant and immediate reduction of MenC incidence was consistently observed in vaccine eligible ages in all countries with high vaccine uptake. The reduction in non-vaccine eligible ages (especially population > 65 years) through herd protection was generally observed 3-4 years following introduction. Vaccine effectiveness (VE) was mostly assessed through screening methods and ranged from 38 to 100%. The VE was generally highest during the first year after vaccination and waned over time. The VE was better maintained in countries employing catch-up campaigns in older children and adolescents, compared to routine infant only schedules. CONCLUSIONS: MCCV were highly effective, showing a substantial and sustained decrease in MenC invasive meningococcal disease. The epidemiology of meningococcal disease is in constant transition, and some vaccination programs now include adolescents and higher valent vaccines due to the recent increase in cases caused by serogroups not covered by MCCV. Continuous monitoring of meningococcal disease is essential to understand disease evolution in the setting of different vaccination programs.

Immunogenicity of a Meningococcal B Vaccine during a University Outbreak.

BACKROUND: In December 2013, a multicomponent meningococcal serogroup B (4CMenB) vaccine was used before licensure on the basis of special consideration by the Food and Drug Administration to respond to an outbreak of Neisseria meningitidis B at a U.S. university. Data suggested that vaccination would control the outbreak because isolates expressed antigens that were closely related to the vaccine antigens (factor H-binding protein [fHbp] and neisserial heparin-binding antigen). We quantified the immune responses induced by 4CMenB during the outbreak. METHODS: We conducted a seroprevalence survey among students to assess vaccination status and collect serum specimens to quantify titers of serum bactericidal antibodies (SBA) with an assay that included human complement (hSBA). We compared the proportion of vaccinated and unvaccinated participants who were seropositive for the outbreak strain and for one closely related reference strain (44/76-SL, which included fHbp) and one mismatched reference strain (5/99, which included neisserial adhesin A), both of which were used in vaccine development. Seropositivity was defined as an hSBA titer of 4 or higher. RESULTS: Among the 499 participants who received two doses of the 4CMenB vaccine 10 weeks apart, 66.1% (95% confidence interval [CI], 61.8 to 70.3) were seropositive for the outbreak strain, although the geometric mean titer was low at 7.6 (95% CI, 6.7 to 8.5). Among a random subgroup of 61 vaccinees who also received two doses but did not have a detectable protective response to the outbreak strain, 86.9% (95% CI, 75.8 to 94.2) were seropositive for the 44/76-SL strain, for which there was a geometric mean titer of 17.4 (95% CI, 13.0 to 23.2), whereas 100% of these vaccinees (95% CI, 94.1 to 100) were seropositive for the 5/99 strain and had a higher geometric mean titer (256.3; 95% CI, 187.3 to 350.7). The response to the outbreak strain was moderately correlated with the response to the 44/76-SL strain (Pearson's correlation,0.64; P<0.001) but not with the response to the 5/99 strain (Pearson's correlation,-0.06; P=0.43). CONCLUSIONS: Eight weeks after the second dose of the 4CMenB vaccine was administered, there was no evidence of an hSBA response against the outbreak strain in 33.9% of vaccinees, although no cases of meningococcal disease caused by N. meningitidis B were reported among vaccinated students. (Funded by Princeton University and others.).

Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England.

Serum samples from children immunized with a meningococcal serogroup B vaccine demonstrated potent serum bactericidal antibody activity against the hypervirulent Neisseria meningitidis serogroup W strain circulating in England. The recent introduction of this vaccine into the United Kingdom national immunization program should also help protect infants against this endemic strain.

An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 2015.

The 23rd World Scout Jamboree in 2015 took place in Japan and included over 33,000 scouts from 162 countries. Within nine days of the meeting ending, six cases of laboratory-confirmed invasive serogroup W meningococcal disease occurred among scouts and their close contacts in Scotland and Sweden. The isolates responsible were identical to one-another by routine typing and, where known (4 isolates), belonged to the ST-11 clonal complex (cc11) which is associated with large outbreaks and high case fatality rates. Recent studies have demonstrated the need for high-resolution genomic typing schemes to assign serogroup W cc11 isolates to several distinct strains circulating globally over the past two decades. Here we used such schemes to confirm that the Jamboree-associated cases constituted a genuine outbreak and that this was due to a novel and rapidly expanding strain descended from the strain that has recently expanded in South America and the United Kingdom. We also identify the genetic differences that define the novel strain including four point mutations and three putative recombination events involving the horizontal exchange of 17, six and two genes, respectively. Noteworthy outcomes of these changes were antigenic shifts and the disruption of a transcriptional regulator.

Polysaccharide-specific memory B cells generated by conjugate vaccines in humans conform to the CD27+IgG+ isotype-switched memory B Cell phenotype and require contact-dependent signals from bystander T cells activated by bacterial proteins to differentiate into plasma cells.

The polysaccharides (PS) surrounding encapsulated bacteria are generally unable to activate T cells and hence do not induce B cell memory (BMEM). PS conjugate vaccines recruit CD4(+) T cells via a carrier protein, such as tetanus toxoid (TT), resulting in the induction of PS-specific BMEM. However, the requirement for T cells in the subsequent activation of the BMEM at the time of bacterial encounter is poorly understood, despite having critical implications for protection. We demonstrate that the PS-specific BMEM induced in humans by a meningococcal serogroup C PS (Men C)-TT conjugate vaccine conform to the isotype-switched (IgG(+)CD27(+)) rather than the IgM memory (IgM(+)CD27(+)) phenotype. Both Men C and TT-specific BMEM require CD4(+) T cells to differentiate into plasma cells. However, noncognate bystander T cells provide such signals to PS-specific BMEM with comparable effect to the cognate T cells available to TT-specific BMEM. The interaction between the two populations is contact-dependent and is mediated in part through CD40. Meningococci drive the differentiation of the Men C-specific BMEM through the activation of bystander T cells by bacterial proteins, although these signals are enhanced by T cell-independent innate signals. An effect of the TT-specific T cells activated by the vaccine on unrelated BMEM in vivo is also demonstrated. These data highlight that any protection conferred by PS-specific BMEM at the time of bacterial encounter will depend on the effectiveness with which bacterial proteins are able to activate bystander T cells. Priming for T cell memory against bacterial proteins through their inclusion in vaccine preparations must continue to be pursued.

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.

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.

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.

National and regional differences in meningococcal vaccine recommendations for individuals at an increased risk of meningococcal disease.

INTRODUCTION: Invasive meningococcal disease (IMD) is a severe, life-threatening condition caused by infection with Neisseria meningitidis. Currently available vaccines offer protection against the five most common meningococcal disease-causing serogroups and include monovalent and quadrivalent conjugate vaccines (MenA, MenC, MenACWY vaccines) and outer membrane vesicle- and/or recombinant protein-based vaccines (MenB vaccines). AREAS COVERED: Country and regional immunization programs target populations susceptible to IMD and typically emphasize the highest-risk age groups (i.e., infants, adolescents/young adults, and the elderly); however, additional groups are also considered at an elevated risk and are the focus of the current review. Specific increased-risk groups include individuals with underlying immunocompromising medical conditions, university/college students, Indigenous people, laboratory workers, military personnel, men who have sex with men, and travelers to areas with hyperendemic IMD. This review compares established meningococcal vaccination recommendations for these vulnerable groups in Europe, the United States, Australia, New Zealand, Israel, Brazil, and Turkey. EXPERT OPINION: Recommendations should be standardized to cover all groups at increased risk of IMD.

Real-world impact and effectiveness of MenACWY-TT.

In response to escalating cases of serogroup W (MenW) invasive meningococcal disease (IMD), multiple countries introduced quadrivalent conjugate MenACWY vaccines into their national immunization programs (NIPs). Here, we summarize the real-world impact and vaccine effectiveness (VE) data of MenACWY-TT from Chile, England, the Netherlands, and Australia. Incidence rate reductions (IRRs) and VE from baseline to post-NIP period were extracted from publications or calculated. After the administration of a single dose of MenACWY-TT, substantial IRRs of MenCWY were observed across the countries in vaccine-eligible age groups (83%-85%) and via indirect protection in non-vaccine-eligible age groups (45%-53%). The impact of MenACWY-TT was primarily driven by MenW IRRs, as seen in vaccine-eligible age groups (65%-92%) and non-vaccine-eligible age groups (41%-57%). VE against MenW was reported in vaccine-eligible toddlers (92%) in the Netherlands and in vaccine-eligible adolescents/young adults (94%) in England. These real-world data support the implementation and continued use of MenACWY-TT in NIPs.

Assessing the Role of Infant and Toddler MenACWY Immunisation in the UK: Does the Adolescent MenACWY Programme Provide Sufficient Protection?

A combined Haemophilus influenzae type b (Hib)/meningococcal serogroup C (MenC) vaccine will soon be unavailable in the UK immunisation schedule due to discontinuation by the manufacturer. An interim statement by the Joint Committee on Vaccination and Immunisation (JCVI) advises stopping MenC immunisation at 12 months of age when this occurs. We undertook an analysis of the public health impact of various potential meningococcal vaccination strategies in the UK in the absence of the Hib/MenC vaccine. A static population-cohort model was developed evaluating the burden of IMD (using 2005-2015 epidemiological data) and related health outcomes (e.g., cases, cases with long-term sequelae, deaths), which allows for the comparison of any two meningococcal immunisation strategies. We compared potential strategies that included different combinations of infant and/or toddler MenACWY immunisations with the anticipated future situation in which a 12-month MenC vaccine is not used, but the MenACWY vaccine is routinely given in adolescents. The most effective strategy is combining MenACWY immunisation at 2, 4, and 12 months of age with the incumbent adolescent MenACWY immunisation programme, resulting in the prevention of an additional 269 IMD cases and 13 fatalities over the modelling period; of these cases, 87 would be associated with long-term sequelae. Among the different vaccination strategies, it was observed that those with multiple doses and earlier doses provided the greatest protection. Our study provides evidence suggesting that the removal of the MenC toddler immunisation from the UK schedule would potentially increase the risk of unnecessary IMD cases and have a detrimental public health impact if not replaced by an alternate infant and/or toddler programme. This analysis supports that infant and toddler MenACWY immunisation can provide maximal protection while complementing both infant/toddler MenB and adolescent MenACWY immunisation programmes in the UK.

Meningococcal Disease in the Post-COVID-19 Era: A Time to Prepare.

The global invasive meningococcal disease (IMD) landscape changed considerably during the COVID-19 pandemic, as evidenced by decreased incidence rates due to COVID-19 mitigation measures, such as limited social contact, physical distancing, mask wearing, and hand washing. Vaccination rates were also lower during the pandemic relative to pre-pandemic levels. Although policymakers may have shifted their focus away from IMD vaccination programs to COVID-19 vaccination programs, strong arguments support implementation and prioritization of IMD vaccination programs; IMD cases have increased in some countries and IMD rates may even have exceeded pre-pandemic levels. Additional concerns include increased susceptibility due to vaccination coverage gaps, increased incidence of other respiratory pathogens, immunity debt from lockdown restrictions, and increased IMD epidemiologic variability. The full range of benefits of widely available and effective meningococcal vaccines needs to be considered, especially in health technology assessments, where the broad benefits of these vaccines are neither accurately quantified nor captured in implementation policy decisions. Importantly, implementation of meningococcal vaccination programs in the current IMD climate also appeals to broader healthcare principles, including preparedness rather than reactive approaches, generally accepted benefit-risk approaches to vaccination, historical precedent, and the World Health Organization's goal of defeating meningitis by 2030. Countries should therefore act swiftly to bolster existing meningococcal vaccination strategies to provide broad coverage across age groups and serogroups given the recent increases in IMD incidence.

Invasive meningococcal capsular group Y disease, England and Wales, 2007-2009.

Enhanced national surveillance for invasive meningococcal disease in England and Wales identified an increase in laboratory-confirmed capsular group Y (MenY) disease from 34 cases in 2007 to 44 in 2008 and 65 in 2009. For cases diagnosed in 2009, patient median age at disease onset was 60 years; 39% of patients had underlying medical conditions, and 19% died. MenY isolates causing invasive disease during 2007-2009 belonged mainly to 1 of 4 clonal complexes (cc), cc23 (56% of isolates), cc174 (21%), cc167 (11%), and cc22 (8%). The 2009 increase resulted primarily from sequence type 1655 (cc23) (22 cases in 2009, compared with 4 cases each in 2007 and 2008). cc23 was associated with lpxL1 mutations and meningitis in younger age groups (<25 years); cc174 was associated with nonmeningitis, particularly pneumonia, in older age groups (>65 years). The increase in MenY disease requires careful epidemiologic and molecular monitoring.

Correlates of protection for meningococcal surface protein vaccines: lessons from the past.

INTRODUCTION: Recombinant surface protein meningococcal serogroup B (MenB) vaccines are available but with different antigen compositions, leading to differences between vaccines in their immunogenicity and likely breadth of coverage. The serology and breadth of coverage assessment for MenB vaccines are multifaceted areas, and a comprehensive understanding of these complexities is required to appropriately compare licensed vaccines and those under development. AREAS COVERED: In the first of two companion papers that comprehensively review the serology and breadth of coverage assessment for MenB vaccines, the history of early meningococcal vaccines is considered in this narrative review to identify transferable lessons applicable to the currently licensed MenB vaccines and those under development, as well as their serology. EXPERT OPINION: Understanding correlates of protection and the breadth of coverage assessment for meningococcal surface protein vaccines is significantly more complex than that for capsular polysaccharide vaccines. Determination and understanding of the breadth of coverage of surface protein vaccines are clinically important and unique to each vaccine formulation. It is essential to estimate the proportion of MenB cases that are preventable by a specific vaccine to assess its overall potential impact and to compare the benefits and limitations of different vaccines in preventing invasive meningococcal disease.

Correlates of protection for meningococcal surface protein vaccines: current approaches for the determination of breadth of coverage.

INTRODUCTION: The two currently licensed surface protein non-capsular meningococcal serogroup B (MenB) vaccines both have the purpose of providing broad coverage against diverse MenB strains. However, the different antigen compositions and approaches used to assess breadth of coverage currently make direct comparisons complex. AREAS COVERED: In the second of two companion papers, we comprehensively review the serology and factors influencing breadth of coverage assessments for two currently licensed MenB vaccines. EXPERT OPINION: Surface protein MenB vaccines were developed using different approaches, resulting in unique formulations and thus their breadth of coverage. The surface proteins used as vaccine antigens can vary among meningococcal strains due to gene presence/absence, sequence diversity, and differences in protein expression. Assessment of the breadth of coverage provided by vaccines is influenced by the ability to induce cross-reactive functional immune responses to sequence diverse protein variants; the characteristics of the circulating invasive strains from specific geographic locations; methodological differences in the immunogenicity assays; differences in human immune responses between individuals; and the maintenance of protective antibody levels over time. Understanding the proportion of meningococcal strains, which are covered by the two licensed vaccines, is important in understanding protection from disease and public health use.

Nasopharyngeal colonization by Neisseria lactamica and induction of protective immunity against Neisseria meningitidis.

BACKGROUND: Natural immunity to Neisseria meningitidis may result from nasopharyngeal carriage of closely related commensals, such as Neisseria lactamica. METHODS: We enrolled 61 students with no current carriage of Neisseria species and inoculated them intranasally with 10,000 colony-forming units of Neisseria lactamica or sham control. Colonization was monitored in oropharyngeal samples over 6 months. We measured specific mucosal and systemic antibody responses to N. lactamica and serum bactericidal antibody (SBA) and opsonophagocytic antibodies to a panel of N. meningitidis serogroup B strains. We also inoculated an additional cohort following vaccination with N. lactamica outer-membrane vesicles (OMV) produced from the same strain. RESULTS: Twenty-six (63.4%) of 41 inoculated individuals became colonized with N. lactamica; 85% remained colonized at 12 weeks. Noncarriers were resistant to rechallenge, and carriers who terminated carriage were relatively resistant to rechallenge. No carriers acquired N. meningitidis carriage over 24 weeks, compared with 3 control subjects (15%). Carriers developed serum IgG and salivary IgA antibodies to the inoculated N. lactamica strain by 4 weeks; noncarriers and control subjects did not. Cross-reactive serum bactericidal antibody responses to N.meningitidis were negligible in carriers, but they developed broad opsonophagocytic antimeningococcal antibodies. OMV vaccinees developed systemic and mucosal anti-N. lactamica antibodies and were relatively resistant to N. lactamica carriage but not to natural acquisition of N. meningitidis. CONCLUSIONS: Carriers of N. lactamica develop mucosal and systemic humoral immunity to N. lactamica together with cross-reacting systemic opsonophagocytic but not bactericidal antibodies to N. meningitidis. Possession of humoral immunity to N. lactamica inhibits acquisition of N. lactamica but not of N. meningitidis. Some individuals are intrinsically resistant to N. lactamica carriage, independent of humoral immunity.

Kinetics of immune responses to nasal challenge with meningococcal polysaccharide one year after serogroup-C glycoconjugate vaccination.

BACKGROUND: Recipients of serogroup-C glycoconjugate meningococcal vaccine (MCC) exhibit waning of serum bactericidal antibody (SBA) titers, but the rate of decline and the speed of their immunological memory in response to new meningococcal nasopharyngeal colonization are unknown. METHODS: In a prospective challenge study, we measured persistence of SBA and anti-Neisseria meningitidis serogroup-C (MenC) immunoglobulin (Ig) G and IgA in adults aged 18-39, 28 days and 12 months after receiving MCC. Volunteers were then challenged intranasally with 50 µg MenC polysaccharide to mimic meningococcal colonization, and systemic and mucosal antibody responses were measured. RESULTS: All subjects had protective SBA titers (≥8) 28 days after MCC vaccination, but 12.3% and 20.2% had unprotective (<8) or low (<128) levels, respectively, after 12 months. Following rechallenge (12 months postvaccination) and measurement of antibody responses after 4, 7, and 10 days, rises in SBA titers were only observed in subjects with low (<128) or nonprotective (<8) prerechallenge SBA titers. In subjects with pre rechallenge SBA titers <8, the majority did not reach a protective SBA titer until 7 days post-rechallenge. MenC-specific IgG levels rose in both serum and saliva in correlation with SBA titers. No detectable rise in salivary IgA was observed. CONCLUSIONS: In those individuals who fail to retain protective SBA 12 months after MCC, immunological memory fails to generate protective systemic and mucosal antibodies until 7 days post intranasal challenge with cognate meningococcal polysaccharide. This is likely too slow to protect from natural meningococcal infection. MCC vaccinees rely on persistence of antibody levels rather than immunological memory for sustained protection.

Review of clinical studies comparing meningococcal serogroup C immune responses induced by MenACWY-TT and monovalent serogroup C vaccines.

Many countries are replacing meningococcal serogroup C (MenC) conjugate vaccines (MCCV) with quadrivalent conjugate (MenACWY) vaccines, such as MenACWY-TT (Nimenrix®). This review examined eight studies comparing MenC immune responses induced by MenACWY-TT and MCCV to determine if these data support these changes. MenC serum bactericidal antibody levels using human (hSBA) or rabbit complement (rSBA) were evaluated at ~1 month postvaccination. Overall, ≥98.4% of infants administered 2 + 1 MenACWY-TT or MCCV schedules had rSBA titers ≥1:8 postprimary and postbooster vaccination; hSBA titers ≥1:8 were similar. In toddlers administered single MenACWY-TT or MCCV doses, ≥97.3% had rSBA titers ≥1:8 postvaccination; percentages with hSBA titers ≥1:8 were higher post-MenACWY-TT. Of children and adolescents receiving primary and booster MenACWY-TT and MCCV, ≥98.6% had rSBA titers ≥1:8; all children receiving MenACWY-TT or MCCV booster had hSBA titers ≥1:8 postdosing. MenC immune responses induced by MenACWY-TT are robust and generally comparable/superior to MCCV, supporting changes to recommendations.