Meningitis is inflammation of the meninges, the lining which surrounds the brain. The disease should not be confused with encephalitis which is inflammation of the brain itself. Essentially, there are two distinct types of meningitis; aseptic (usually caused by viral infections) and bacterial. Bacterial meningitis, while it is comparatively rare, is by far the most dangerous and is sometimes fatal. As such, it gets the most media attention, but the Foundation is acutely aware of the effects of the more common viral meningitis. Most of the current vaccine efforts are directed toward preventing bacterial meningitis cases since these so often lead to death or disability in survivors.
Meningitis B Bexsero Package insert – Approved in Europe and Australia used in Princeton New Jersey outbreak
September 20, 2019 – Up-to-date coverage with meningococcal vaccine among adolescents age 17 years: Patterns and correlates in the United States, 2017
• Few studies have explored patterns of up-to-date (UTD) MenACWY coverage in the US.
• UTD MenACWY coverage lags behind all other adolescent vaccines.
• Coverage is higher among black and Hispanic adolescents and those living in the Northeast.
• School entry requirements but not exemption policies were associated with UTD MenACWY coverage.
• 13% of adolescents had a missed opportunity for UTD MenACWY.
January 2, 2018 – Meningococcal carriage among a university student population – United States, 2015 “Meningococcal carriage was associated with being male, smoking, party or club attendance, recent antibiotic use (inverse correlation), and recent respiratory infections. Conclusions In this university setting, the majority of meningococcal carriage was due to nongroupable strains, followed by serogroup B. Further evaluation is needed to understand the dynamics of serogroup B carriage and disease among university students.
December 14, 2017 – Post-licensure safety surveillance study of routine use of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (full text)
Table 4. Investigation of significantly elevated events.
| Event category | Findings |
|---|---|
| Diabetes, type 1 | 5 cases, all with onset prior to vaccination: Events occurring on days 38 through 165. |
| Difficulty breathing/shortness of breath | 9 events were distributed between days 6 and 154, with a mean latency of 82 days and median latency of 61 days. There was no obvious pattern to the distribution. |
| Elective procedure | Not researched further. |
| Febrile illness | 47 events: 4 events on day 1; 1 event on day 5; 3 events on day 125; 2 events each on days 121, 137 and 180; occasional other days with 1 case. Fever is a known common adverse event following vaccination. |
| Genital pain | 5 events: Dysmenorrhea on days 16 and 135; ovarian cyst on day 90; unspecified male genital disorder on day 129; menometrorrhagia on day 171. There was no obvious pattern to the distribution of events in time. On review, they were disparate in type, so we did not investigate further. |
| Hives/urticaria | 51 events in the 11–16 year age group were distributed between days 2 and 180, with an average latency of 93 days and a median latency of 95 days. |
| Hyperglycemia | 6 events: Days 4, 16, 126, 130, 150 and 168. There was no obvious pattern to the distribution and we did not investigate further. |
| Mononucleosis | There were 5 events, all in the 17–18 year old age group, where such an incidence can be expected. |
| Otitis external | 5 events: Days 20, 22, 66, 82, and 119. |
| Suicidal ideation/attempt | All events of suicide ideation/attempt for which records were available (5/6) revealed risk factors prior to vaccination (e.g., prior attempts, depression, stressors, alcohol abuse). |
| Tympanic perforation | All events represented planned tympanoplasty surgeries. |
| Vomiting | The range of days for 39 events was between day 1 and 178, with an average latency of 96 days and a median latency of 97 days. There was no obvious pattern associated with these vomiting cases; they appear to be evenly distributed within the interval, with >1 event of vomiting occurring on only six days (days 76, 113, 124, 127, 171, and 177). One case of vomiting occurred the day after vaccination which was considered to be related to receipt of MenACWY-D. |
Conclusions: This study did not detect any safety concerns following MenACWY-D and provides reassurance that MenACWY-D administered as part of routine care was not associated with unexpected safety risks
March 8, 2016 – Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines “The wide-range use of this protein in massive vaccine production requires constant increase of production yields and adaptability to an ever-growing market. Here we compare CRM197 with the alternative diphtheria non-toxic variant DT-K51E/E148K, an inactive mutant that can be produced in the periplasm of Escherichia coli.“…”Overall, our data indicate that DT-K51E/E148K is a readily produced protein that now allows the added flexibility of E. coli production in vaccine development and that can be effectively used as protein carrier for a meningococcal conjugate vaccine.”
February 24, 2016 – Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine in healthy adolescents in Korea—A randomised trial “Conclusions Two doses of 4CMenB induced robust immune responses against the vaccine antigens and were well tolerated, with no safety concerns identified, in Korean adolescents (NCT01973218). Also, see other adverse events. Other Adverse Events
Serious Adverse Events
| rMENB | Placebo/MenACWY | Total | |
|---|---|---|---|
| Total, serious adverse events | |||
| # participants affected / at risk | 2/174 (1.15%) | 0/88 (0.00%) | 2/262 (0.76%) |
| Infections and infestations | |||
| GASTROENTERITIS * 1 | |||
| # participants affected / at risk | 1/174 (0.57%) | 0/88 (0.00%) | 1/262 (0.38%) |
| Reproductive system and breast disorders | |||
| PAROVARIAN CYST * 1 | |||
| # participants affected / at risk | 1/174 (0.57%) | 0/88 (0.00%) | 1/262 (0.38%) |
February 2016 – Immunogenicity and Safety of a 3- and 4-dose Vaccination Series of a Meningococcal ACWY Conjugate Vaccine in Infants: Results of a Phase 3b, Randomized, Open-label Trial “Four subjects withdrew from the study prematurely because of AEs: 1 subject in the ACWY3 group (Krabbe disease on day 117 after the third vaccination), 1 in the routine group (bronchiolitis on day 14 after the first vaccination) and 2 subjects in the ACWY4 group (both experienced convulsions). Of the 2 infants experiencing convulsions, the first suffered a severe seizure on day 38 after the fourth study vaccination and the second subject suffered a potential mild seizure on day 2 after the third study vaccination (this subject also suffered 2 SAEs of severe bronchiolitis—on day 17 after the first vaccination and day 46 after the second vaccination—both of which required hospitalization and a third SAE of a severe asthma attack on day 95 after the third vaccination).”
January 27, 2016 – Adolescent, parent and societal preferences and willingness to pay for meningococcal B vaccine: A Discrete Choice Experiment “Vaccine effectiveness, adverse events and duration of immunity are important drivers for parental and adolescent decisions about WTP for MenB vaccine and should be included in discussions on the benefits, risks and cost.
January 25, 2016 – An update on immunization in UK “The immunization schedule changes frequently and it is important that healthcare professionals keep up to date. Parents often look to specialists for advice about vaccinating their children and place more trust in them, than government bodies. This article describes the introduction of meningococcal B and ACWY vaccines and the extension of influenza vaccine to some older children.”
January 2016 – Severe Upper Extremity Dysfunction After 4CMenB Vaccination in a Young Infant “Therefore, the vaccine may enter soon nationwide vaccine recommendation schemes. We report on a case of a 5-month-old infant who developed prolonged upper extremity dysfunction after the second injection of the 4CMenB vaccine in the left deltoid muscle and was concomitantly applied with 2 routine vaccinations. Myositis, periostitis, (peri-) vasculitis and axillary inflammation were confirmed by magnetic resonance imaging. Two months after initial initiation of an anti-inflammatory and an antibiotic treatment, symptoms completely resolved. Administration of 3 vaccines requires clear recommendations for the preferred injection site in infants because increased reactogenicity of 4CMenB may lead to local severe adverse events.”
January 2016 – Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration “Conclusions:
Volume 15, Issue 1, 2016 – Update on the use of meningococcal serogroup C CRM197-conjugate vaccine (Meningitec) against meningitis “It appears that Meningitec has a less favorable immunologic profile compared particularly to tetanus toxoid (TT) MenC conjugate vaccines.Data from comparative trials have raised interesting questions on priming of the immune system by conjugate vaccines, particularly in infants. The results from these and other studies are reviewed here with specific focus on Meningitec.”
November 27, 2015 – Vaccines for prevention of group B meningococcal disease: Not your father’s vaccines “Recently, however, two new vaccines have been licensed for prevention of group B disease. Although immunogenic and considered to have an acceptable safety profile, there are many scientific unknowns about these vaccines, including effectiveness against antigenically diverse endemic meningococcal strains; duration of protection; whether they provide any herd protection; and whether there will be meningococcal antigenic changes that will diminish effectiveness over time. In addition, these vaccines present societal dilemmas that could influence how they are used in the U.S., including high vaccine cost in the face of a historically low incidence of meningococcal disease.”
November 9, 2015 – Effect of age on the incidence of aseptic meningitis following immunization with monovalent mumps vaccine (full tex)”Although all of the subjects included in this study received the mumps vaccines as a first dose, most countries that include a mumps-containing vaccine in their immunization programs required two doses that were administered at 3 to 6 years after the first dose. The pre-existence of immunity may have had a direct impact on the incidences of adverse events following immunization. However, there is little information on the safety of the second dose of mumps vaccine. Further studies are necessary to investigate the efficacy and safety of the second dose of these mumps vaccines.”
September 30, 2015 – The introduction of the meningococcal B (MenB) vaccine (Bexsero®) into the national infant immunisation programme – New challenges for public health “Since the vaccine only protects against 73–88% of circulating MenB strains in England, clinical isolates and PCR-positive samples will require extensive characterisation by the Meningococcal Reference Unit (MRU) at Public Health England (PHE) in order to monitor vaccine effectiveness and identify potential vaccine failures.
September 16, 2015 – Severe Upper Extremity Dysfunction After 4CMenB Vaccination in a Young Infant. “We report the case of a 5-month-old infant who developed prolonged upper extremity dysfunction after the 2nd injection of the 4CMenB vaccine in the left deltoid muscle along with two concomitantly applied routine vaccinations. Myositis, periostitis, (peri-) vasculitis and axillar inflammation was confirmed by magnetic resonance imaging. Two months after initial initiation of anti-inflammatory and antibiotic treatment symptoms resolved completely. Administration of three vaccines requires clear recommendations for the preferred injection site in infants, since increased reactogenicity of 4CMenB might lead to local severe adverse events.
August 3, 2015 – Coadministration of a 9-Valent Human Papillomavirus Vaccine With Meningococcal and Tdap Vaccines “This study in 11- to 15-year-old boys and girls compared the immunogenicity and safety of GARDASIL 9 (9-valent human papillomavirus [9vHPV] vaccine) administered either concomitantly or nonconcomitantly with 2 vaccines routinely administered in this age group (Menactra [MCV4; Neisseria meningitidis serotypes A/C/Y/W-135] or Adacel [Tdap; diphtheria/tetanus/acellular pertussis]).”…”Concomitant administration of 9vHPV vaccine with MCV4/Tdap was generally well tolerated and did not interfere with the antibody response to any of these vaccines. This strategy would minimize the number of visits required to deliver each vaccine individually.”
July 9, 2015 – Vaccination against serogroup B Neisseria meningitidis: Perceptions and attitudes of parents “The spontaneous acceptance rate of vaccination against serogroup B meningococcal invasive disease is insufficient. However, after objective information by their physician or public health authorities, only a few parents would in the end be completely resistant.”
May 21, 2015 – MATS: Global coverage estimates for 4CMenB, a novel multicomponent meningococcal B vaccine (full text) “In 2013, there were two outbreaks of meningococcal serogroup B disease at US universities – at Princeton University and the University of California Santa Barbara. Isolates from these outbreaks were tested by the CDC and GSK laboratories and were predicted as covered by 4CMenB. The CDC and FDA implemented a program under an expanded access Investigational New Drug (IND) Protocol, over 14,000 students have received 4CMenB and subsequently, 4CMenB received Breakthrough status by the US FDA and. 4CMenB was approved for use in individuals from 10 to 25 years of age by the FDA in January of 2015.”…”Global estimates of 4CMenB strain coverage ranged from 66% to 91%, per country. MATS will be used in post-implementation surveillance to monitor the effectiveness and coverage of 4CMenB over time.”
April 27, 2015 – First Use of a Serogroup B Meningococcal Vaccine in the US in Response to a University Outbreak (pdf) “Although the number of sporadic cases of serogroup B meningococcal disease occurring in adolescents each year is at historic lows, the potential impact of MenB vaccines on both sporadic disease and outbreaks will be important to consider in the development of recommendations for use of licensed MenB vaccines in the United States.”…”POTENTIAL CONFLICT OF INTEREST: Dr Johnsen was invited by Pfizer (manufacturer of rLP2086, Trumenba) to speak to their vaccine group and at 3 national conferences. Pfizer paid for Dr Johnsen’s airfare and lodging to attend these events; he did not receive an honorarium or other reimbursements. Dr Johnsen was also invited by the National Meningitis Association to participate in a round table at another conference. The National Meningitis Association paid for Dr Johnsen’s lodging but did not provide any honorarium or other reimbursements.”
April 9, 2015 – The diversity of meningococcal carriage across the African meningitis belt and the impact of vaccination with a group A meningococcal conjugate vaccine (pdf) “Carriage was more prevalent in males than females, perhaps because of more frequent social mixing among young adult males than females in Muslim societies, more prevalent in rural than in urban areas and in those exposed to smoke, either from cigarettes or from cooking. Development of less polluting methods of cooking is a priority for many parts of the developing world and could contribute to a reduction in the incidence of meningococcal infection as well as of pneumonia. The absence of an association between carriage and recent respiratory symptoms contrasts with findings from studies in Burkina Faso. The lack of any association with attendance at social gatherings was inconsistent with findings from the UK, where social behaviour was closely linked to risk of carriage.”
- Competing interests Helen Findlow reports performing contract research on behalf of Public Health England for Novartis Vaccines and Diagnostics, Baxter Biosciences and GlaxoSmithKline.
- Ray Borrow reports performing contract research on behalf of Public Health England for Novartis Vaccines and Diagnostics, Pfizer, Baxter Biosciences, Sanofi Pasteur, Serum institute of India and GlaxoSmithKline.
- Caroline Trotter reports receiving a consulting payment from GSK. None of the other authors declare a conflict of interest.
- Funding The work of the MenAfriCar Consortium is supported by grants from the Bill & Melinda Gates Foundation and from the Wellcome Trust. Nicole Basta is supported by NIH grant DP5OD009162.
April 1, 2015 – An unusual occurrence of Kleine-Levin syndrome in a man with refractory immune thrombocytopenic purpura: a case report (full text) “Kleine-Levin syndrome is an extremely rare neurological entity characterized by recurrent episodes of hypersomnia which are sometimes associated with compulsive hyperphagia and behavioral changes. Autoimmunity has recently been proposed as a factor contributing to its pathogenesis. Immune thrombocytopenic purpura is a relatively common autoimmune disease showing a lot of complexity and uncertainty regarding its treatment regimens and its refractory nature in some cases. A 32-year-old Persian White man visited his private hematologist complaining of recent episodes of epistaxis and appearance of petechial lesions 24 hours after receiving a meningococcal vaccine”
April 1, 2015 – Immunogenicity of reduced dose priming schedules of serogroup C meningococcal conjugate vaccine followed by booster at 12 months in infants: open label randomised controlled trial (full text) “In the absence of any infant MenC vaccine priming doses, the protection provided by just one MenC vaccine dose administered at 12 months of age would strongly rely on the persistence of herd protection, induced by a previous catch up MenC immunisation campaign, which could then be maintained by a booster in adolescence.”
March–April, 2015 – Why Are U.S. Girls Getting Meningococcal But Not Human Papilloma Virus Vaccines? Comparison of Factors Associated with Human Papilloma Virus and Meningococcal Vaccination Among Adolescent Girls 2008 to 2012 “However, White girls were 10% more likely to report provider recommendation than Black or Hispanic girls (p < .01), yet did not have higher vaccination rates, implying a role for parental refusal. No factors predicted consistently the completion of the HPV vaccine series among those who started.”…”Improving provider recommendation for co-administration of HPV and meningococcal vaccines would reduce missed opportunities for initiating the HPV vaccine series. However, different interventions may be necessary to improve series completion.”
March 30, 2015 – Vaccine hesitancy among parents of adolescents and its association with vaccine uptake “We determined the vaccination status of the parents’ adolescents for 3 vaccines (Tetanus–diphtheria–acellular pertussis [Tdap], meningococcal conjugate [MCV4], and human papillomavirus [HPV] vaccines). We used Fisher’s exact tests to compare vaccination status with each survey item and with an overall general hesitancy scale that we constructed. Results We analyzed 363 surveys. At the time of the visit, vaccination coverage was 84% for Tdap, 73% for MCV, and 45% for any dose of HPV. Thirty-nine percent of parents expressed concern about vaccine efficacy and 41% expressed concern about side effects. Forty-five percent of parents disagreed with the statement that “teens can get all of the vaccines that are due at a single visit.”
March 27, 2015 – Waning antibody levels seen in children who received meningococcal B vaccine as infants (full text) “The Novartis vaccine (Bexsero) and Pfizer’s meningococcal group B vaccine, Trumenba, which are approved in Europe and other countries, were recently approved in the United States. At a meeting in February, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended serogroup B meningococcal vaccination for several groups at increased risk for serogroup B disease, including students during outbreaks at college campuses. Broader use of these vaccines in adolescents and college students is on the agenda of the next ACIP meeting in June 2015.”…”The study was sponsored by Novartis, manufacturer of the vaccine. Author disclosures include being an investigator for studies funded by vaccine manufacturers, including Novartis and GlaxoSmithkline, and serving as consultants and advisors for those manufacturers. Three authors are Novartis employees.”
March 6, 2015 – Update on Vaccination Guidelines for Older Adults “The number of infections covered and the types of vaccines available has grown significantly in recent years. Although this represents tremendous progress, it can also result in confusion and missed opportunities to provided recommended vaccinations. This review summarizes the current guidelines for vaccination of older adults and highlights the latest innovations.”…”Generalizing vaccine guidelines for adults and implementing them in practice is more complicated than for childhood vaccines. A range of co-morbidities may affect vaccine recommendations; for instance, there are no age-specific recommendations for Haemophilus influenzae or meningococcus vaccination, although they are recommended in all asplenic adults. There is the practical hurdle of understanding payer responsibility and reimbursement, and there is the challenge of understanding the potential benefits and limitations of a vaccine.
December 26, 2014 – Progressive Decrease in the Potential Usefulness of Meningococcal Serogroup B Vaccine (4CMenB, Bexsero®) in Gipuzkoa, Northern Spain (full text) “The incidence of meningococcal disease in our region has substantially declined in the last decade, and most recent circulating isolates lacked antigens against which vaccinated people would have been protected. In the current situation, and considering the high incidence of fever from the vaccine, the introduction of the 4CMenB vaccine in our community does not seem to achieve the necessary priority to be recommended. If an outbreak caused by a hypervirulent clone were to occur, especially if the clone was the ST11 clone, the vaccine would be extremely useful.”
December 13, 2014 – Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial (full text) “We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18–24-year-olds.”…”Significa
November 2014 – Antibody Persistence After Primary and Booster Doses of a Quadrivalent Meningococcal Conjugate Vaccine in Adolescents (full text) “After licensure of MenACWY-D, additional evidence indicated that many adolescents might not be protected for more than 5 years.5 Therefore, since
2010, ACIP has recommended a booster dose of MenACWY at age 16 years so that adolescents immunized at 11–12 years continue to be protected throughout the period of high disease risk (16–21 years).2,5″ Comment: What’s next after 21? To get or keep employment, or insurance you will need to be vaccinated?
October 17, 2014 – A quadrivalent vaccine against serogroup B meningococcal disease: a cost-effectiveness study “If the vaccine is able to disrupt carriage acquisition, greater decreases in cases can be achieved through vaccination. In the short-term, this is best achieved through routine infant vaccination, and in the long term strategies including routine adolescent vaccination result in higher and sustained reductions in cases over the long term. Infant strategies alone, with or without indirect effects, have limited impact and cannot be considered cost effective.”
October 1, 2014 – Survey of pediatricians in Germany reveals important challenges for possible implementation of meningococcal B vaccination (full text) “Incidence of invasive meningococcal disease is low in Germany at 0.5 cases/100,000 inhabitants.”…”
July 21, 2014 – Preventing secondary cases of invasive meningococcal capsular group B (MenB) disease using a recently-licensed, multi-component, protein-based vaccine (Bexsero®) “Even in the most favourable scenario where we assume the vaccine is administered within 4 days of the index case and prevents 90% of cases occurring after 14 days, the NNV for household contacts was >1000. NNV in educational settings was much higher.”
July 7, 2014 – Increasing Provision of Adolescent Vaccines in Primary Care: A Randomized Controlled Trial “At the 5-month follow-up, AFIX consultations increased vaccine coverage among younger adolescents. Patients in the in-person arm experienced coverage changes that exceeded those in the control arm for Tdap (3.4% [95% confidence interval (CI): 2.2 to 4.6]), meningococcal (4.7% [95% CI: 2.3 to 7.2], and HPV (1.5% [95% CI: 0.3 to 2.7]) vaccines. Patients in the webinar versus control arm also experienced larger changes for these vaccines. AFIX did little to improve coverage among older adolescents.”…”AFIX consultations for adolescents need improvement to have a stronger and more durable impact, especially for HPV vaccine.”
July 2014 – Persistence of Bactericidal Antibodies to 5 Years of Age After Immunization With Serogroup B Meningococcal Vaccines at 6, 8, 12 and 40 Months of Age (full text) “Waning immunity before the age of 5 years is particularly important as the incidence of MenB disease remains higher in 1- to 4-year-old children, second only to that of children <1 year. These data suggest that by the time children immunized in infancy or at 40 months enter primary school they may no longer have immunity to a number of MenB strains and this vulnerability is therefore likely to extend into adolescence. Further follow-on studies will be required to assess whether this is also true for those immunized at 60 months. This is of particular interest because MenB disease has a second smaller peak in late teenage years, therefore these results give an early indication that an adolescent booster may be required.”
May 08, 2014 – Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: A randomized, open-label, multi-center study “MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs.” Comment: Wow, without compromising the vaccine?
March 2014 – UK poised to make decision on 4CMenB vaccine (full text) “In a letter to The Lancet shortly after the JCVI’s interim statement, Steve Black, a paediatrician based at Cincinnati Children’s Hospital in Ohio, USA, pointed to the failure of modelling to predict the cost effectiveness of several vaccines before their introduction in the USA. Most strikingly, the cost per quality-adjusted life-year saved by the pneumococcal conjugate vaccine was estimated to be more than US$80 000 in the prelicensure cost effectiveness analysis, but the actual cost was shown to be ten-times lower when the true effects of the vaccine were known after it was introduced.”…”“Novartis had placed great expectations on the UK, because the country has had a progressive meningitis C vaccination programme”, says Timo Vesikari, of the University of Tampere Medical School in Finland and a lead investigator on several clinical trials of 4CMenB. “The meningitis B problem in the UK is at least of the same magnitude as meningitis C was when the vaccination programme was started in 1999”, he continues. That programme, says Moxon, was introduced with no population-based efficacy study, no knowledge of herd immunity, and no economic analysis preceding its adoption for routine use. And yet, he contends, it has been “one of public health’s great success stories”.
March 2014 – Vaccine Eligibility in Hospitalized Children: Spotlight on a Unique Healthcare Opportunity “One hundred sixty pediatric patients ages 2 months to 17 years (mean age 8 years) were enrolled. Seventy-six percent of patients had documentation of vaccine history, and 92% were documented as receiving all age-appropriate vaccines. Actual immunization records showed that 16% percent of patients were in compliance with Advisory Committee on Immunization Practices guidelines. The most commonly missed vaccine was influenza (67%) followed by meningococcal (57%), hepatitis A (48%), and varicella (38%). Ninety percent of parents were satisfied with the vaccination services their child had received.”
February 26, 2014 – Distribution of invasive meningococcal B disease in Italian pediatric population: Implications for vaccination timing (full text) “The present work provided country specific data which can be an important key point, as suggested by international recommendations to make sustainable decisions, given the great regional variability in MenB incidence and serogroup distribution. Since the available vaccine is made of a mix of 4 subcapsular protein of MenB, which can be absent in different MenB isolates, it will be mandatory to go on with epidemiological studies to evaluate whether, under the immune pressure induced by vaccination, new mutants which do not express the 4 proteins target of the vaccine will escape the immune system. Large epidemiological studies will continue to be needed to monitor and evaluate the introduction of this new vaccine, and to measure the impact of vaccination on achieving the goal of eliminating meningococcal disease and RT-PCR should be included in all surveillance programs in order to obtain more precise evaluation of incidence, case fatality rate and serogroup distribution.” Comment: So from the introduction of the vaccine they are using a faulty vaccine also, one that will change the bacterial population by using it.
January 23, 2014 – A Consensus Statement: Meningococcal Disease among Infants, Children and Adolescents in Latin America “Because of the crowded infant immunization schedule, the development of combined meningococcal vaccines and the co-administration with other infant vaccines should be explored.”
January 16, 2014 – Immunisation against meningococcus B: the case of Spain (full text) “First, from a public health perspective, the 4CMenB vaccine is surrounded by several uncertainties regarding safety, clinical effectiveness, and laboratory surveillance and monitoring, which, together with the decreasing trend in the incidence of invasive meningococcal B disease in Spain, warrant a cautious decision regarding the use of this vaccine in a routine programme at present and reserving it for specific high-risk situations (such as outbreaks) and for immunosuppressed patients.
January 9, 2014 – Parental and community acceptance of the benefits and risks associated with meningococcal B vaccines“There is strong community support for introduction of Men B vaccines, with parental willingness to have children immunised, impacted more by number of injections than potential for adverse events such as local reactions or fever.”
December 17, 2013 – Diversity of Canadian meningococcal serogroup B isolates and estimated coverage by an investigational meningococcal serogroup B vaccine (4CMenB) (full text) “While our active population-based sentinel surveillance data provide the most comprehensive measurement of IMD in Canada, several limitations apply. MenB IMD is rare and the numbers in any given age group or province are small; therefore our ability to detect differences among subgroups is limited, and differences in strain coverage among age or geographic groups were not statistically significant. Approximately 20% of MenB cases in our data were confirmed by PCR only with no isolate available for testing. Additionally, IMPACT surveillance includes primarily urban areas of Canada and may not be representative of remote or rural regions.”
November 7, 2013 – Immunisation against meningococcus B: the case of Spain “Alongside France and the UK, Spain adds to the list of countries adopting a wait-and-see approach. In Spain, not even a rigorous cost-benefit assessment was deemed necessary to support the decision, and some hasty calculations of disability-adjusted life-years have been considered sufficient. As in other European countries, the incidence of meningococcal B disease in Spain is at its lowest level in decades.”…”The wait-and-see approach is saving money but costing lives. I have received funding for research and consultancy from Novartis and manufacturers of other meningococcal vaccines.”
October 2013 – Bactericidal Antibody Persistence 2 Years After Immunization With 2 Investigational Serogroup B Meningococcal Vaccines at 6, 8 and 12 Months and Immunogenicity of Preschool Booster Doses: A Follow-on Study to a Randomized Clinical Trial “Conclusions: Bactericidal antibodies wane after infant immunization with rMenB or 4CMenB, but there is an anamnestic response to a booster dose. Booster doses of 4CMenB may be required to maintain immune protection through childhood and adolescence.”
September 23, 2013 – Persistence of bactericidal antibodies following early infant vaccination with a serogroup B meningococcal vaccine and immunogenicity of a preschool booster dose “As has been observed with other meningococcal vaccines, bactericidal antibodies waned after vaccination with 4CMenB administered according to an approved infant vaccination schedule of 2, 4, 6 and 12 months of age, but there was an anamnestic response to a booster dose at 40–44 months of age.”
September 23, 2013 – Effectiveness of meningococcal serogroup C vaccine programmes “Studies have demonstrated that MCC vaccination confers protection in infancy (0–12 months) from the first dose but this is only short-term. NeisVac-C® has the greatest longevity of the currently licensed MCC vaccines in terms of antibody persistence, however antibody levels have been found to fall rapidly after early infant vaccination with two doses of all MCC vaccines – necessitating a booster at ∼12 months. In toddlers, only one dose of the MCC vaccine is required for routine immunization. If herd protection wanes following catch-up campaigns, many children may become vulnerable to infection. This has led many to question whether an adolescent booster is also required.”
September 7, 2013 – Immunisation against meningococcus B – by Stanley A Plotkin “There is another aspect that should concern us. Considering that the development of a new vaccine costs at least half a billion US dollars, vaccine manufacturers must make choices. Bodies like the JCVI and ACIP should give prospective advice to manufacturers about which vaccines are of interest and will be recommended. This is not a question of protecting profits by manufacturers, but rather the reality that only a limited number of vaccines can be developed, and it is in the interests of all of us that development leads to widespread use and control of disease. I have received honoraria and consultancies from major vaccines manufacturers, including Novartis, Sanofi, and GSK.
July 2013 – Seroprevalence and Placental Transmission of Maternal Antibodies Specific for Neisseria meningitidis Serogroups A, C, Y and W135 and Influence of Maternal Antibodies on the Immune Response to a Primary Course of MenACWY-CRM Vaccine in the United Kingdom (full text) “A.J.P. has conducted clinical trials on behalf of Oxford University, sponsored by Wyeth/Pfizer Vaccines, GlaxoSmithKline Vaccines, Sanofi Pasteur, Sanofi Pasteur MSD and Novartis Vaccines and organized educational meetings at Oxford University with unrestricted grants from these manufacturers, but does not accept any personal payments from vaccine manufacturers. M.D.S. has received assistance to attend scientific meetings from Wyeth Vaccines, Novartis Vaccines and GlaxoSmithKline Vaccines and has had travel and accommodation expenses paid by Novartis Vaccines while working in collaboration with Novartis Vaccines, Siena, Italy. M.D.S. has also conducted clinical trials on behalf of Oxford University, sponsored by Pfizer, Sanofi Pasteur and GlaxoSmithKline. D.F.K. has received assistance from GSK and Wyeth to attend scientific meetings and funding for research from GSK. P.M.D. is an employee of Novartis Vaccines.”…”Conclusions: The levels of serogroup-specific meningococcal antibodies were low in mothers and 2-month-old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.”
July, 2013 – One or Two Doses of Quadrivalent Meningococcal Serogroups A, C, W-135 and Y Tetanus Toxoid Conjugate Vaccine Is Immunogenic in 9- to 12-Month-Old Children (full text) GlaxoSmithKline Biologicals SA was the funding source and was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals SA also funded all costs associated with the development and the publishing of the present article. All authors had full access to the data, and the corresponding author was responsible for submission of the publication.”…”Adverse events leading to an ER visit were reported by 10.6% and 16.9% of subjects in the ACWY-1 and ACWY-2 group, respectively. Seventeen subjects (10.6%) in the ACWY-1 group had at least 1 ER visit during the study. The most common diagnoses associated with the ER visits were infections (upper respiratory tract infection, viral infection, croup) as well as dehydration, pyrexia, febrile convulsion and injuries. An ER visit was reported by 32 subjects (16.9%) in the ACWY-2 group. The most common diagnoses were diarrhea, vomiting and pyrexia, as well as infections (gastroenteritis, pneumonia, upper respiratory tract infection and viral infection) and injuries. No deaths occurred during the study. In order to identify whether the longer follow-up period contributed to the greater number of adverse event reports after vaccination in the ACWY-2 group, we conducted a post hoc analysis considering only adverse events reported after the second dose of ACWY-TT to study end (ie, 6 monthsextended safety follow-up) on subjects who received 2 vaccine doses (N = 172). The following adverse events were reported during the 6-month period from 12 to 18 months of age: any SAEs (0.6%), new onset of chronic disease (18.0%), rash (23.3%) and ER visits (11.0%) (Table 3).”
May 11, 2013 – Single priming dose of meningococcal group C conjugate vaccine (NeisVac-C®) in infants “With new vaccines continually being added to many national pediatric vaccination schedules, the reduction of vaccination doses can increase the general acceptability of the immunization strategies among targeted parental communities. The need to maximize protection of children and especially infants against Neisseria meningitidis serogroup C with as few vaccine doses as possible has led to additional clinical studies comparing the safety and immunogenicity profiles of different vaccination schedules.”
March 5, 2013 – Immune response, antibody persistence, and safety of a single dose of the quadrivalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine in adolescents and adults: results of an open, randomised, controlled study (pdf) “Non-inferiority of the MenACWY-TT vaccine over the MenACWY polysaccharide vaccine, in terms of incidence of solicited and unsolicited grade 3 general symptoms reported within four days after vaccination, was demonstrated. Of note, clinically relevant severe general symptoms and vaccine-related events are most likely to occur during the four-day post-vaccination period. However, the incidence of any grade 3 symptoms seemed higher in the participants who received the MenACWY-TTvaccine than the MenACWY polysaccharide vaccine and this observation was driven by the local injection site reactions. The specifically solicited injection site redness and swelling with any intensity were also more frequently reported in the participants who received the MenACWY-TT vaccine than the MenACWY polysaccharide vaccine. These observations are likely due to the TT content of the conjugate vaccine and are consistent with previous studies showing that local reactions are more frequent in individuals vaccinated with quadrivalent meningococcal conjugate vaccines compared to plain polysaccharide vaccines.”
March 4, 2013 – Persistence of antibodies in laboratory staff immunized with quadrivalent meningococcal polysaccharide vaccine (pdf) “Average duration of protection in adults immunized with meningococcal polysaccharide vaccine reaches ten years or more. Due to considerable inter-individual variability protection falls below the average estimate in a substantial proportion of adults immunized with polysaccharide formulations. Specifically, immunity against serogroup W135 may last less than five years, the period suggested by CDC [13] and UK’s Department of Health [10] for reimmunization, for approximately 23% of vaccinees. Thus, presented observations may contribute to reconsideration of the presently recommended periods for revaccination of adults at risk for occupational infection.”
March 2013 – Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials “At 12 months of age, waning titers were boosted by a fourth dose, such that 95—100% of children had hSBA titres of 5 or more for all antigens, with or without concomitant MMRV. Immune responses to routine vaccines were much the same with or without concomitant 4CMenB, but concomitant vaccination was associated with increased reactogenicity. 77% (1912 of 2478) of infants had fever of 38·5°C or higher after any 4CMenB dose, compared with 45% (295 of 659) after routine vaccines alone and 47% (228 of 490) with MenC, but only two febrile seizures were deemed probably related to 4CMenB.”
March 2013 – The beginning of the end for serogroup B meningococcus? “the persisting threat posed by serogroup B Neisseria meningitidis (MenB) is an unwelcome anomaly. This organism’s external polysaccharide capsule is poorly immunogenic, sharing chemical and antigenic identity with human fetal neural-cell antigens.
October 5, 2012 – Immunogenicity and safety of a new meningococcal A conjugate vaccine in Indian children aged 2–10 years: A Phase II/III double-blind randomized controlled trial “None of the adverse events or serious adverse events was related to the study vaccines. We conclude that MenAfriVac™ is well tolerated and significantly more immunogenic when compared to a licensed polysaccharide vaccine, in 2-to-10-year-old Indian children.”
July 20, 2012 – Evolution of immune response against Neisseria meningitidis B:14:P1.7,16 before and after the outer membrane vesicle vaccine MenBvac “The percentage of hSBA titer ≥4 was 10.8% before vaccination, raised to 84.1% 6 weeks after the completion of the schedule, but declined to 39.7% one year later. This level is lower than the targeted 60% level and suggests only short-term persistence of response against B:14:P1.7,16 using this schedule.”
June 14, 2012 – Approval Letter – MenHibrix – Menhibrix package Insert (pdf) “In addition to the pivotal studies, safety data are available from 4 studies which either did not include a fourth dose of MENHIBRIX, used a dosing regimen not approved in the United States,, or incorporated a comparator vaccine which was not licensed in the United States. In these studies, participants were monitored for unsolicited adverse events and serious adverse events occurring in the 31–day period following vaccination. In 2 of these studies, participants were monitored for serious adverse events, new onset chronic disease, rash, and conditions prompting emergency department visits or physician office visits through 6 months after the last vaccination. Solicited Adverse Events: The reported frequencies of solicited local and systemic adverse events from US participants in Study 009/010 are presented in Table 1. Because of differences in reported rates of solicited adverse events between US and non-US participants, only the solicited adverse event data in US participants are presented.Among the US participants included in Table 1, 48% were female; 76% were white, 10% were black, 4% were Hispanic, 2% were Asian, and 8% were of other racial/ethnic groups.
May 30, 2012 – Prevalence of Serum Bactericidal Antibody to Serogroup C Neisseria meningitidis in England a Decade after Vaccine Introduction “Antibody levels and effectiveness waned quickly in children vaccinated at 2, 3, and 4 months of age. Therefore, in 2006, the current revised schedule of doses at 3, 4, and 12 months was introduced. This study assessed age-specific protection in 2009 compared with data from historical prevaccination and early postvaccination studies.”
May 10, 2012 – The Effect of Human Factor H on Immunogenicity of Meningococcal Native Outer Membrane Vesicle Vaccines with Over-Expressed Factor H Binding Protein (full text) “Development of conjugate vaccines against group B strains, however,has been hampered by cross-reactivity of the group B polysaccharide with host molecules, and safety concerns about the potential to elicit auto-reactive antibodies. Development of a vaccine against group B strains is important since these strains are responsible for about one-third of cases of meningococcal disease in the U.S. and up to 90% in some European countries.
April 30, 2012 – Adverse events following immunization during mass vaccination campaigns at first introduction of a meningococcal A conjugate vaccine in Burkina Faso, 2010. “Convulsions, urticaria and bronchospasm were more frequently reported. Attack rates for those conditions were similar to the baseline rates recorded in the same population, over the same time period, a year earlier. With the exception of convulsions in the days following vaccination the distribution of time intervals between vaccination and the occurrence of symptoms did not reveal any temporal clustering. The monitoring of AEFI of MenAfriVac™ in Burkina Faso did not suggest special concern regarding the vaccine safety. However, reported possible hypersensitivity reactions to vaccine components would require further review to rule out any anaphylactic reaction.”
August 2011– IOM Adverse Effects of Vaccines Evidence and Causality (full text) “Evidence Convincingly Supports a Causal Relationship: The MMR vaccine is linked to a disease called measles inclusion body encephalitis, which in very rare cases can affect people whose immune systems are compromised and usually occurs within a year of acute measles infection or vaccination. The MMR vaccine also is linked to febrile seizures, which are a type of seizure that occurs in infants and young children in association with fever. Febrile seizures are generally benign and hold no long-term consequences. Six types of vaccines—MMR, varicella zoster, influenza, hepatitis B, meningococcal, and tetanus containing vaccines—are linked to anaphylaxis. The committee also found convincing evidence of a causal relationship between injection of vaccine, independent of the antigen involved, and two types of adverse events, including syncope, or fainting, and deltoid bursitis, or frozen shoulder, characterized by shoulder pain and loss of motion.”
February 23, 2011 – Battle Brewing Over Mandatory Meningitis Vaccine
July 6, 2010 – Are Doctors Giving Patients the Best Vaccines, or the Vaccines With the Best Price? “For example, Sanofi Pasteur, which markets the meningitis vaccine Menactra, bars doctors from offering Novartis’s vaccine, Menveo, even though some studies indicate Menveo may offer greater protection to teenagers.”
January 8, 2008 – Investigational Vaccine Effective Against Meningitis in Infancy “The researchers noted that the study was too small to draw firm conclusions on the safety of the vaccine. Further studies are also needed to confirm that the vaccine does not interact with the pneumococcal glycoconjugate vaccine, which uses the same protein carrier, they said.”
January 8, 2008 – New Meningitis Vaccine Works in Infants Menveo not available in US yet, British researchers note “Novartis is currently conducting phase III clinical trials on the vaccine and hopes to begin the licensing procedure in the United States sometime in 2008, though it would still be a few more years before any vaccine would be commercially available in this country.”
October 29, 2007 – Wider Age Range for Meningitis Vaccine “On October 18, 2007, FDA approved expanding the age range for Menactra, a bacterial meningitis vaccine, to include children ages 2 to 10 years. The vaccine was first approved by FDA in January 2005 for people ages 11 to 55 years. Until now, Menomune was the only meningococcal vaccine available in the United States for use in children ages 2 and older. Menactra and Menomune are manufactured by Sanofi Pasteur Inc. of Swiftwater, Pa.”