MeNZB: a safe and highly immunogenic tailor-made vaccine against the New Zealand Neisseria meningitidis serogroup B disease epidemic strain

Clinical studies have been conducted in New Zealand evaluating the safety and immunogenicity of an outer membrane vesicle (OMV) vaccine, MeNZB, developed to control epidemic disease caused by group B meningococci, subtype P1.7b,4. MeNZB, administered in a three-dose regimen, was well tolerated and induced a seroresponse, defined as a four-fold rise (> or =titre 8) in serum bactericidal antibodies against the vaccine strain 4-6 weeks after the third vaccination, in 96% (95% confidence interval (CI): 79-100%) of adults, 76% (95% CI: 72-80%) of children, 75% (95% CI: 69-80%) of toddlers and 74% (95% CI: 67-80%) of infants receiving MeNZB. In conclusion, these findings suggest that MeNZB is safe and is likely to confer protection against systemic group B meningococcal disease caused by the epidemic strain.     

Evaluating the post-licensure effectiveness of a group B meningococcal vaccine in New Zealand: a multi-faceted strategy

A nationwide strategy to control a group B meningococcal disease epidemic in New Zealand using an epidemic strain-specific vaccine (MeNZB ) commenced in 2004. In the absence of randomised controlled trials investigating the efficacy of this particular vaccine, a complement of observational methods are planned to evaluate the post-licensure effectiveness of this vaccine strategy. The two main approaches involve a Poisson regression model investigating the overall impact of the MeNZB programme on disease rates over time capitalising on detailed population-based disease surveillance data and the staged roll-out of the vaccine campaign, and a case-control study that aims to estimate vaccine effectiveness in pre-school children. The studies are designed to minimise the potential biases inherent in all observational methods and provide critical data on the effectiveness of a major public health intervention.     

From secondary prevention to primary prevention: a unique strategy that gives hope to a country ravaged by meningococcal disease

New Zealand has been affected by an epidemic of group B meningococcal disease dominated by a strain defined as, B:4:P1.7b,4. Over 5550 cases and 222 deaths have been reported since 1991 in a population of 4 million people.Meningococcal disease cases notified on EpiServ database operated by Institute of Environmental Science and Research Limited through to 30 September 2004. Through the collaborative efforts of a government agency, vaccine company, university and laboratory institute, clinical trials of the Chiron produced outer membrane vesicle (OMV) strain-specific MeNZB vaccine were run in rapid succession. The delivery of MeNZB will be New Zealand's largest immunisation programme with three doses given at 6-week intervals to over 1 million people aged 6 weeks-19 year olds inclusive. Planning, co-ordinating and delivering the immunisation programme is a challenging project for the New Zealand Health Sector.     

Vaccine Preventability of Meningococcal Clone,Greater Aachen Region,Germany

Emergence of serogroup B meningococci of clonal complex sequence type (ST) 41/44 can cause high levels of disease, as exemplified by a recent epidemic in New Zealand. Multiplication of annual incidence rates (3.1 cases/100,000 population) of meningococcal disease in a defined German region, the city of Aachen and 3 neighboring countries (Greater Aachen) prompted us to investigate and determine the source and nature of this outbreak. Using molecular typing and geographic mapping, we analyzed 1,143 strains belonging to ST41/44 complex, isolated from persons with invasive meningococcal disease over 6 years (2001–2006) from 2 German federal states (total population 26 million) and the Netherlands. A spatially slowly moving clone with multiple-locus variable-number tandem repeat analysis type 19, ST42, and antigenic profile B:P1.7–2,4:F1–5 was responsible for the outbreak. Bactericidal activity in serum samples from the New Zealand MeNZB vaccination campaign confirmed vaccine preventability. Because this globally distributed epidemic strain spreads slowly, vaccination efforts could possibly eliminate meningococcal disease in this area.     

A prospective study of the effectiveness of the New Zealand meningococcal B vaccine

The effectiveness of a new group B strain-specific meningococcal vaccine referred to as "MeNZB," developed by Chiron Vaccines (Siena, Italy) in collaboration with the Norwegian Institute of Public Health, was assessed in a prospective observational study following a nationwide vaccination program in New Zealand. The vaccination program began in July 2004, and the study uses data from January 2001 to June 2006. A generalized estimating equation model was used to estimate vaccine effectiveness that included potential confounding variables, such as disease progression over time, age, ethnicity, socioeconomic status, seasonality, and geographic region. The model provides strong statistical evidence for a vaccine effect (p < 0.0001), with estimated disease rates 3.7 times higher in the unvaccinated group than in the vaccinated group (95% confidence interval: 2.1, 6.8) and a vaccine effectiveness of 73% (95% confidence interval: 52, 85). An estimated 54 epidemic strain meningococcal cases were prevented in the 2 years since the vaccination program began (95% confidence interval assuming a fixed population size: 22, 115). In a sensitivity analysis, these estimates proved to be robust to modeling assumptions, including population estimates, estimates of the numbers vaccinated, effects of partial vaccination, and temporal autocorrelation.     

Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control

As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.     

Impact of vaccination during an epidemic of serogroup C meningococcal disease in Salvador, Brazil

To combat rising incidence of serogroup C meningococcal disease in the city of Salvador, Brazil, the Bahia state immunization program initiated routine childhood immunization with meningococcal C conjugate vaccine (MenC) in February 2010, followed by mass MenC vaccination of city residents 10-24 years of age from May through August 2010. We analyzed trends in incidence of reported cases of meningococcal disease and serogroup distribution among meningococcal isolates identified in hospital-based surveillance in Salvador from January 2000 to December 2011 and estimated vaccine effectiveness using the screening method. Annual incidence of serogroup C meningococcal disease increased from 0.1 cases per 100,000 population during 2000-2006 to 2.3 in 2009 and 4.1 in 2010, before falling to 2.0 per 100,000 in 2011. Estimated coverage of mass vaccination reached 80%, 67% and 41% among 10-14, 15-19 and 20-24 year olds, respectively. Incidence in 2011 was significantly lower than average rates in 2008-2009 among children <5 years, but reductions among 10-24 year olds were not significant. Among 10-24 year olds, a single dose of MenC vaccine was 100% effective (95% confidence interval, 79-100%) against serogroup C meningococcal disease. Low coverage in the population targeted for mass vaccination may have limited impact on ongoing transmission of serogroup C meningococcal disease despite high vaccine effectiveness.     

Immunogenicity and safety of a strain-specific MenB OMV vaccine delivered to under 5-year olds in New Zealand

To control the devastating group B meningococcal epidemic in New Zealand a strain-specific OMV vaccine (MeNZB) was extensively tested before vaccination of >1,000,000 people under 20 years. After the three-dose course 75% of 6-8-month-old infants and 16-24-month-old toddlers showed four-fold increases in bactericidal antibodies. In 6-10-week-old infants a fourth dose was needed to obtain similar results. After primary vaccination, the antibody titre decline was most pronounced among the youngest but both young infants and toddlers showed a clear booster response to a fourth dose. MeNZB was safe and well tolerated. The comprehensive post-licensure safety surveillance revealed no safety concerns.     

Effectiveness of a trivalent serogroup A/C/W135 meningococcal polysaccharide vaccine in Burkina Faso, 2003

Following a large Neisseria meningitidis W135 (NmW135) epidemic in Burkina Faso (BF) during 2002, a newly licensed trivalent A/C/W135 meningococcal polysaccharide vaccine was introduced in 2003. We conducted a case-control study to assess the vaccine effectiveness (VE) against meningococcal disease. Thirty-two N. meningitidis A (NmA) and 3 NmW135 meningitis cases were enrolled and matched by age-neighborhood to 103 controls. After adjusting for confounding risk factors, VE against NmA or NmW135 was 83.6% (95% CI 31.8-97.0, p=0.01) for persons with verified vaccination. VE against probable/definite NmA alone was 94.0% (95% CI 58.7-99.0, p=0.0003). Low number of NmW135 cases did not allow estimation of VE against NmW135 alone. The vaccine was highly effective against the epidemic. Since 2003, the trivalent vaccine continues to be effectively used in Africa for the control of meningococcal disease epidemics.     

Carriage of a new epidemic strain of Neisseria meningitidis and its relationship with the incidence of meningococcal disease in Galicia, Spain

In Galicia, Spain, a dramatic increase in the incidence of meningococcal disease was seen in the 1995-6. The annual incidence rose to 11 per 10(5) inhabitants, and 80% of identified strains were C:2b:P1.2,5. This led to the implementation of an intensive A+C vaccination campaign for the population aged 18 months to 19 years. During this campaign the prevalence of carriage in areas with high and low incidence was studied. Nasopharyngeal swabs were taken from 9796 subjects immediately before the administration of meningococcal vaccine, plated onto Thayer-Martin plates, incubated and sent for analysis to the Reference Laboratory for Neisseria in Spain. The prevalence of the C:2b: P1.2,5 strains was 0.6% (95% CI 0.29-0.88) in the high incidence area, and 0.41% (95 % CI 0.00-1.04) in the low incidence area, and that of serogroup C (all strains) 1.36% (95% CI 0.80-1.80) and 0.89% (95% CI 0.09-1.69) respectively. The prevalence of N. meningitidis (all strains) was almost the same in both areas (8%). Carriers of the epidemic strain were not found in the 2-4 year age group, that most affected by the disease. Our data showed a wide distribution but a low carriage rate of the epidemic strain C:2b:P1.2,5 in the high and low disease incidence areas studied; the difference in the carriage rates between the two areas was not statistically significant.     

New Zealand's epidemic of meningococcal disease described using molecular analysis: implications for vaccine delivery

New Zealand's epidemic of meningococcal disease began in mid 1991. Surveillance of meningococcal disease in New Zealand is based on a combination of disease notification and organism characterisation. Case numbers and population rates rose from 53 (1.5 per 100,000 population) in 1990 to a high of 650 (17.4 per 100,000 population) in 2001. The highest rates of disease occur in Pacific peoples under 20 years but the highest percentages of cases occur in Maori and European New Zealanders. The epidemic has been driven by a strain identified as B:4:P1.7b,4, ST-41/44 complex/Lineage III. The stability of the P1.7b,4 Por A protein has been demonstrated suggesting that the epidemic may be controlled by a strain-specific OMV vaccine.     

High predicted strain coverage by the multicomponent meningococcal serogroup B vaccine (4CMenB) in Poland

Neisseria meningitidis of serogroup B (MenB) is currently responsible for more than 70% of cases of invasive meningococcal disease (IMD) in Poland and Europe as a whole. The aim of this study was to estimate strain coverage of a multicomponent meningococcal serogroup B vaccine (4CMenB) in Poland; the meningococcal antigen typing system (MATS) was used to test a panel of 196 invasive MenB strains isolated in Poland in 2010 and 2011. The strains were also characterized by MLST and sequencing of porA, factor H-binding protein (fHbp), Neisserial heparin-binding antigen (nhba) and Neisserial adhesin A (nadA) genes. MATS and molecular data were analyzed independently and in combination. The MATS results predicted that 83.7% (95% CI: 78.6–91.0%) of isolates would be covered by the 4CMenB vaccine; 59.2% by one vaccine antigen, 19.9% by two and 4.6% by three antigens. Coverage by each antigen was as follows: fHbp 73.0% (95% CI: 68.9–77.5%), NHBA 28.6% (95% CI: 13.3–47.4%), NadA 1.0% (95% CI: 1.0–2.0%) and PorA 10.2%. Molecular analysis revealed that the most frequent clonal complexes (ccs) were cc32 (33.2%), cc18 (17.9%) and cc41/44 (15.8%) with estimated coverage of 98.5%, 88.6% and 93.5%, respectively.Consistent with findings for other European countries, our study predicts high coverage by the 4CMenB vaccine in Poland.     

Serogroup A,C, W,and Y meningococcal disease in persons previously vaccinated with a serogroup ACWY meningococcal vaccine – United States, 2014–2018

BackgroundThe Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination with a quadrivalent meningococcal conjugate serogroup A,C,W,Y (MenACWY) vaccine at 11–12 years of age, with a booster dose at 16 years. ACIP also recommends meningococcal vaccination for persons at increased risk of meningococcal disease, including a 2-dose primary series and regular booster doses for persons at increased risk because of underlying medical conditions. U.S. cases of serogroup A, C, W, and Y meningococcal disease in persons previously vaccinated with MenACWY vaccine have not been systematically described since 2008. Characterization of these cases is important to understand potential factors leading to breakthrough disease.MethodsWe analyzed cases of serogroup A,C,W, and Y meningococcal disease reported through the National Notifiable Diseases Surveillance System (NNDSS) from 2014 through 2018. State health departments submitted additional information on risk factors and clinical course.ResultsDuring 2014–2018, 822 cases of serogroup A, C, W, and Y meningococcal disease were reported through NNDSS; 34 (4%) were in patients who previously received ≥ 1 dose of MenACWY vaccine. Twenty-three vaccinated patients were up-to-date on MenACWY vaccine per recommendations, and seven were not up-to-date; four were missing information on the number of doses received. Seventeen cases (50%) occurred > 3 years after the most recent dose. A significantly higher proportion of vaccinated patients were people living with HIV (PLWH) compared to unvaccinated patients. Eight of the 34 vaccinated patients were immunosuppressed, including five PLWH, one taking eculizumab, and two taking other immunosuppressive medications. The case fatality ratio did not differ between vaccinated and unvaccinated patients.ConclusionsImmunosuppression, incomplete vaccination, and waning immunity likely contributed to breakthrough cases of meningococcal disease among people who received MenACWY vaccine. Continued monitoring of serogroup A, C, W, and Y meningococcal disease in previously vaccinated persons will help inform meningococcal disease prevention efforts.     

流脑A群多糖菌苗划片免疫九年流行病学效果观察

据预测1984年前后保定市为流脑大流行高峰年。为预防其出现,于1980~1984年对保定市区1~15岁儿童进行了两轮流脑多糖菌苗的按区划片免疫,接种率达80.01%。1985~1988年只对12~24月龄幼儿进行接种,接种率为97.15%。9年间免疫组观察833 333人发病4人,发病率为0.48/10万;对照组观察304 085人,发病25人,发病率为8.22/10万。菌苗保护率为94.16%,效果指数1:17.12。不仅有效地防止了保定市1984年大流行高峰年而且使1980~1988年连续9年流脑发病率维持在1/10万左右,是历史上最低水平。     

The concept of "tailor-made", protein-based, outer membrane vesicle vaccines against meningococcal disease

Protein-based, outer membrane vesicle (OMV) vaccines have previously proven to be efficacious against serogroup B meningococcal disease in Norway and Cuba. Currently, a public health intervention is going on in order to control a serogroup B epidemic in New Zealand. The scale-up and standardization of vaccine production required for controlling the New Zealand epidemic has allowed the establishment of large-scale GMP manufacturing for OMV vaccines. The outcome of this will be licensing of the vaccine in New Zealand and possibly other countries. The availability of licensed OMV vaccines raises the question of whether such vaccines may provide the opportunity to control other outbreaks and epidemics. For instance, such a vaccine could control a localised outbreak of group B meningococci in Normandy, France. "Tailor-made" vaccines, focusing on the sub-capsular antigens may also be considered for use in sub-Saharan Africa for the prevention of the recurrent outbreaks by serogroups A and W135 meningococci. This assumption is based on the epidemiological observation that meningococcal outbreaks in Africa are clonal and are strikingly stable regarding their phenotypic characteristics.     

Safety review: two outer membrane vesicle (OMV) vaccines against systemic Neisseria meningitidis serogroup B disease

MenBvac is an OMV vaccine against systemic serogroup B Neisseria meningitidis disease. MenBvac was developed for control of a B:15:P1.7,16 subtype epidemic in Norway and administered to 180,000 subjects in 28 clinical studies. MeNZB, a daughter vaccine of MenBvac, was developed for a clonal B:4:P1.7b,4 epidemic in New Zealand and administered to 1 million people <20 years. The vaccines were similar regarding reactogenicity profile. Serious adverse events (SAEs) in general and particularly neurologic SAEs were very rare. Despite frequently reported local reactions and fever in those under 5 years, these OMV-based vaccines containing 25 microg antigen can be considered safe for use in all age groups.     

Vaccination as teenagers against meningococcal disease and the risk of the chronic fatigue syndrome

The etiology of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is unknown. In Norway, a vaccine against Neisseria meningitides group B was administered to teenagers in 1988--1989 in a protection trial. In order to estimate the relative risk of CFS/ME according to vaccine history, we conducted a case-control study in 2007, with 201 cases diagnosed at one of two hospitals and 389 controls. The adjusted odds ratio for CFS/ME was 1.06 (95% CI: 0.67-1.66) for subjects who received the active vaccine contrasted to subjects who did not. Using this design, no statistically significant association between vaccination against meningococcal disease in teenagers and occurrence of CFS/ME could be observed.     

Cohort study of Covid-19 vaccine effectiveness among healthcare workers in Finland,December 2020 - October 2021

Recently, Covid-19 vaccine effectiveness has decreased especially against mild disease due to emergence of the Delta variant and waning protection. In this register-based study among healthcare workers in Finland, the vaccine effectiveness of two-dose mRNA vaccine series against SARS-CoV-2 infection decreased from 82% (95% CI 79–85%) 14–90 days after vaccination to 53% (43–62%) after 6 months. Similar trend was observed for other series. Waning was not observed against Covid-19 hospitalization. These results facilitate decision-making of booster doses for healthcare workers.     

1999-2017年江苏省流行性脑脊髓膜炎流行特征分析

目的 分析1999-2017年江苏省流行性脑脊髓膜炎(简称流脑)的发病流行变化趋势,为有效预防控制流脑提供参考依据。方法 采用描述流行病学方法对1999-2017年江苏省流脑病例的流行情况进行描述和分析。结果 1999-2017年江苏省累计报告流脑病例814例,年均发病率00575/10万,其中2004年发病率最高,2017年降到最低;流脑发病主要集中在15岁以下儿童,占5644%;12月份到次年4月份为流脑发病高峰,占8713%,其中2月发病最多;病例以学生和散居儿童为主,分别占4092%和 2277%;2006-2017年,C群脑膜炎奈瑟菌(Neisseria meningitidis,Nm)是主要流行菌株,占有明确菌群结果的5634%。结论 江苏省流脑发病呈下降趋势,但病死率有所上升,保持较高接种覆盖率,适时对重点地区和重点人群开展流脑疫苗补充免疫,同时加强流脑菌群变迁监测,是控制流脑流行的关键。