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Human Vaccines & Immunotherapeutics 2019Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is characterized by high mortality and morbidity. While IMD incidence peaks in both infants and... (Review)
Review
Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is characterized by high mortality and morbidity. While IMD incidence peaks in both infants and adolescents/young adults, carriage rates are often highest in the latter age groups, increasing IMD risk and the likelihood of transmission. Effective vaccines are available for 5 of 6 disease-causing serogroups. Because adolescents/young adults represent a significant proportion of cases, often have the highest carriage rate, and have characteristically low vaccination adherence, efforts should be focused on educating this population regarding long-term consequences of infection and the importance of meningococcal vaccination in prevention. This review describes the role of adolescents/young adults in meningococcal transmission and the clinical consequences and characteristics of IMD in this population. With a focus on countries with advanced economies that have specific meningococcal vaccination recommendations, the epidemiology of meningococcal disease and vaccination recommendations in adolescents/young adults will also be discussed.
Topics: Adolescent; Humans; Incidence; Meningococcal Infections; Meningococcal Vaccines; Serogroup; Vaccination; Young Adult
PubMed: 30273506
DOI: 10.1080/21645515.2018.1528831 -
Frontiers in Immunology 2019The discovery of vaccine antigens through whole genome sequencing (WGS) contrasts with the classical hypothesis-driven laboratory-based analysis of microbes to identify... (Review)
Review
The discovery of vaccine antigens through whole genome sequencing (WGS) contrasts with the classical hypothesis-driven laboratory-based analysis of microbes to identify components to elicit protective immunity. This radical change in scientific direction and action in vaccine research is captured in the term . The complete genome sequence of an isolate of serogroup B (MenB) was systematically analyzed to identify proteins predicted to be secreted or exported to the outer membrane. This identified hundreds of genes coding for potential surface-exposed antigens. These were amplified, cloned in expression vectors and used to immunize mice. Antisera against 350 recombinant antigens were obtained and analyzed in a panel of immunological assays from which 28 were selected as potentially protective based on the -antibody dependent, complement mediated- serum bactericidal activity assay. Testing of these candidate vaccine antigens, using a large globally representative strain collection of Neisseria species isolated from cases of disease and carriage, indicated that no single component would be sufficient to induce broad coverage and that a "universal" vaccine should contain multiple antigens. The final choice of antigens to be included was based on cross-protective ability, assayed by serum bactericidal activity and maximum coverage of the extensive antigenic variability of MenB strains. The resulting multivalent vaccine formulation selected consisted of three recombinant antigens (Neisserial Heparin Binding Antigen or NHBA, Factor H binding protein or fHbp and Neisseria Adhesin A or NadA). To improve immunogenicity and potential strain coverage, an outer membrane vesicle component obtained from the epidemic New Zealand strain (OMVNz) was added to the formulation to create a four component vaccine, called 4CMenB. A series of phase 2 and 3 clinical trials were conducted to evaluate safety and tolerability and to estimate the vaccine effectiveness of human immune responses at different ages and how these were affected by various factors including concomitant vaccine use and lot-to-lot consistency. 4CMenB was approved in Europe in 2013 and introduced in the National Immunization Program in the UK starting from September 2015 when the vaccine was offered to all newborns using a 2, 4, and 12 months schedule., The effectiveness against invasive MenB disease measured at 11 months after the study start and 5 months after the second vaccination was 83% and there have been no safety concerns.
Topics: Animals; Antigens, Bacterial; Computational Biology; Genes, Bacterial; Humans; Meningitis, Meningococcal; Meningococcal Vaccines; Mice; Neisseria meningitidis, Serogroup B; Vaccines, Synthetic; Vaccinology; Whole Genome Sequencing
PubMed: 31040844
DOI: 10.3389/fimmu.2019.00751 -
Vaccine Jul 2023The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of...
The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.
Topics: Child; Humans; Bacterial Infections; Haemophilus influenzae type b; Haemophilus Vaccines; Meningococcal Vaccines; Norway; Pneumococcal Vaccines; Splenectomy; Vaccination; Vaccines, Conjugate; Guideline Adherence; Vaccination Coverage
PubMed: 37336662
DOI: 10.1016/j.vaccine.2023.06.034 -
Frontiers in Immunology 2018Since it became available as a routine tool in biology, the determination and analysis of nucleotide sequences has been applied to the design of vaccines and the... (Review)
Review
Since it became available as a routine tool in biology, the determination and analysis of nucleotide sequences has been applied to the design of vaccines and the investigation of their effectiveness. As vaccination is primarily concerned with the interaction of biological molecules with the immune system, the utility of sequence data is not immediately obvious and, indeed, nucleotide sequence data are most effective when used to complement more conventional immunological approaches. Here, the impact of sequencing on the field of vaccinology will be illustrated with reference to the development and implementation of vaccines against (the meningococcus) over the 30-year period from the late-1980s to the late-2010s. Nucleotide sequence-based studies have been important in the fight against this aggressive pathogen largely because of its high genetic and antigenic diversity, properties that were only fully appreciated because of sequence-based studies. Five aspects will be considered, the use of sequence data to: (i) discover vaccine antigens; (ii) assess the diversity and distribution of vaccine antigens; (iii) determine the evolutionary and population biology of the organism and their implications for immunization; and (iv) develop molecular approaches to investigate pre- and post-vaccine pathogen populations to assess vaccine impact. One of the great advantages of nucleotide sequence data has been its scalability, which has meant that increasingly large data sets have been available, which has proved invaluable in the investigation of an organism as diverse and enigmatic as the meningococcus.
Topics: Amino Acid Sequence; Animals; Antigenic Variation; Antigens, Bacterial; Biological Evolution; Humans; Meningococcal Infections; Meningococcal Vaccines; Models, Molecular; Neisseria meningitidis; Polysaccharides, Bacterial; Protein Conformation; Sequence Analysis; Structure-Activity Relationship; Vaccines, Conjugate
PubMed: 30697213
DOI: 10.3389/fimmu.2018.03151 -
Journal of Global Health Jun 2019Meningococcal disease continues to be a global public health concern due to its epidemic potential, severity, and sequelae. The global epidemiological data on...
BACKGROUND
Meningococcal disease continues to be a global public health concern due to its epidemic potential, severity, and sequelae. The global epidemiological data on circulating meningococcal serogroups have never been reviewed concurrently with the laboratory capacity for meningococcal surveillance at the national level. We, therefore, aimed to conduct a country-level review of meningococcal surveillance, serogroup distribution, and vaccine use.
METHODS
We conducted a systematic literature review across six databases to identify studies (published January 1, 2010 to October 16, 2017) and grey literature reporting meningococcal serogroup data for the years 2010-2016. We performed independent random effects meta-analyses for serogroups A, B, C, W, X, Y, and other. We developed and circulated a questionnaire-based survey to surveillance focal points in countries (N = 95) with known regional bacterial meningitis surveillance programs to assess their surveillance capacity and summarized using descriptive methods.
RESULTS
We included 173 studies from 59 countries in the final analysis. The distribution of meningococcal serogroups differed markedly between countries and regions. Meningococcal serogroups C and W accounted for substantial proportions of meningococcal disease in most of Africa and Latin America. Serogroup B was the predominant cause of meningococcal disease in many locations in Europe, the Americas, and the Western Pacific. Serogroup Y also caused many cases of meningococcal disease in these regions, particularly in Nordic countries. Survey responses were received from 51 countries. All countries reported the ability to confirm the pathogen in-country, while approximately 30% either relied on reference laboratories for serogrouping (N = 10) or did not serogroup specimens (N = 5). Approximately half of countries did not utilize active laboratory-based surveillance system (N = 22). Nationwide use of a meningococcal vaccine varied, but most countries (N = 36) utilized a meningococcal vaccine at least for certain high-risk population groups, in private care, or during outbreaks.
CONCLUSIONS
Due to the large geographical variations in circulating meningococcal serogroups, each country should continue to be monitored for changes in major disease-causing serogroups in order to inform vaccine and control policies. Similarly, laboratory capacity should be appropriately scaled up to more accurately understand local epidemiology and disease burden, as well as the impact of vaccination programs.
Topics: Global Health; Humans; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Population Surveillance; Serogroup; Surveys and Questionnaires
PubMed: 30603079
DOI: 10.7189/jogh.09.010409 -
The Journal of Infection Dec 2019The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a... (Review)
Review
The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a GMI meeting was held with a multidisciplinary group of experts and representatives from countries within Eastern Europe. Across the countries represented, IMD surveillance is largely in place, with incidence declining in recent decades and now generally at <1 case per 100,000 persons per year. Predominating serogroups are B and C, followed by A, and cases attributable to serogroups W, X and Y are emerging. Available vaccines differ between countries, are generally not included in immunization programs and provided to high-risk groups only. Available vaccines include both conjugate and polysaccharide vaccines; however, current data and GMI recommendations advocate the use of conjugate vaccines, where possible, due to the ability to interrupt the acquisition of carriage. Ongoing carriage studies are expected to inform vaccine effectiveness and immunization schedules. Additionally, IMD prevention and control should be guided by monitoring outbreak progression and the emergence and international spread of strains and antibiotic resistance through use of genomic analyses and implementation of World Health Organization initiatives. Protection of high-risk groups (such as those with complement deficiencies, laboratory workers, migrants and refugees) is recommended.
Topics: Carrier State; Communicable Disease Control; Disease Outbreaks; Disease Transmission, Infectious; Europe, Eastern; Humans; Incidence; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Serogroup
PubMed: 31682877
DOI: 10.1016/j.jinf.2019.10.018 -
Human Vaccines & Immunotherapeutics Aug 2023Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of quadrivalent meningococcal polysaccharide vaccine (MPV ACYW135) compared with quadrivalent meningococcal conjugate vaccine (Menactra®) in Malian children.
Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study compared the safety and immunogenicity of a quadrivalent meningococcal polysaccharide vaccine (MPV-4, MPV ACYW135) and quadrivalent meningococcal ACWY conjugate vaccine (MCV-4, Menactra®). Healthy, 2- to 10-year-old children in Bamako, Mali, were randomized 1:1 to receive one dose of MPV-4 or MCV-4. Safety outcomes were evaluated for 6 months post-immunization. Immunogenicity for all serogroups was assessed for non-inferiority between MPV-4 and MCV-4 30 days post immunization by serum bactericidal antibody assay using baby rabbit complement (rSBA). From December 2020 to July 2021, 260 healthy subjects were consented and randomized. At Day 30 post-immunization, the proportions of subjects with rSBA titers ≥ 128 for all serogroups in the MPV-4 group were non-inferior to those in MCV-4 group. The proportions of subjects with rSBA ≥ 4-fold increase and rSBA titers ≥ 8 for all serogroups were similar among vaccine groups ( > .05). Geometric Mean Titers and Geometric Mean Fold Increases for all serogroups in both vaccine groups were similar ( > .05). Few local and systemic post-immunization reactions of similar severity and duration were observed within 7 days and were similar in both groups ( > .05). All resolved without sequelae. Unsolicited adverse events were similar in both groups regarding relationship to study vaccine, severity and duration. No serious adverse events were reported during the study period. MPV ACYW135 showed a non-inferior immunogenicity profile and a comparable reactogenicity profile to MCV-4 in Malian children aged 2-10 years.: NCT04450498.
Topics: Humans; Meningococcal Vaccines; Vaccines, Conjugate; Neisseria meningitidis; Vaccination; Serogroup; Antibodies, Bacterial; Meningococcal Infections
PubMed: 37401618
DOI: 10.1080/21645515.2023.2230829 -
Expert Review of Vaccines 2023causes invasive meningococcal disease and, globally, significant morbidity, with serogroup B (MenB) being the most common cause of endemic disease and outbreaks in... (Review)
Review
INTRODUCTION
causes invasive meningococcal disease and, globally, significant morbidity, with serogroup B (MenB) being the most common cause of endemic disease and outbreaks in several regions. Extensive use of the four-component serogroup B meningococcal vaccine (4CMenB; Bexsero, GSK) and its inclusion in immunization programs in several countries have generated substantial safety data during the 9 years since its first authorization in 2013.
AREAS COVERED
4CMenB safety data from clinical trials and post-marketing surveillance studies (2011 to 2022), and spontaneously reported adverse events of medical interest from the GSK global safety database. We discuss these safety findings in relation to the benefit of 4CMenB vaccination and implications for further enhancing vaccine confidence.
EXPERT OPINION
4CMenB has been consistently well tolerated across clinical trials and post-licensure surveillance studies, despite a higher incidence of fever reported in infants than with other pediatric vaccines. Surveillance data have not identified any significant safety issues, consistent with an acceptable safety profile of 4CMenB. These findings highlight the need to balance the risk of relatively common, transient, post-immunization fever with the benefit of affording protection that reduces the risk of uncommon but potentially fatal meningococcal infection.
Topics: Infant; Child; Humans; Meningococcal Infections; Meningococcal Vaccines; Serogroup; Neisseria meningitidis, Serogroup B; Neisseria meningitidis
PubMed: 37278390
DOI: 10.1080/14760584.2023.2222015 -
Clinical Infectious Diseases : An... Nov 2015Group A Neisseria meningitidis has been a major cause of bacterial meningitis in the sub-Saharan region of Africa in the meningitis belt. Neisseria meningitidis is an... (Review)
Review
BACKGROUND
Group A Neisseria meningitidis has been a major cause of bacterial meningitis in the sub-Saharan region of Africa in the meningitis belt. Neisseria meningitidis is an encapsulated pathogen, and antibodies against the capsular polysaccharide are protective. Polysaccharide-protein conjugate vaccines have proven to be highly effective against several different encapsulated bacterial pathogens. Purified polysaccharide vaccines have been used to control group A meningococcal (MenA) epidemics with minimal success.
METHODS
A monovalent MenA polysaccharide-tetanus toxoid conjugate was therefore developed. This vaccine was developed by scientists working with the Meningitis Vaccine Project, a partnership between PATH and the World Health Organization.
RESULTS
A high-efficiency conjugation method was developed in the Laboratory of Bacterial Polysaccharides in the Center for Biologics Evaluation and Research and transferred to the Serum Institute of India, Ltd, which then developed methods for purification of the group A polysaccharide and used its tetanus toxoid as the carrier protein to produce the now-licensed, highly effective MenAfriVac conjugate vaccine.
CONCLUSIONS
Although many years of application of meningococcal polysaccharide vaccines have had minimal success in preventing meningococcal epidemics in the meningitis belt of Africa, our collaborative efforts to develop a MenA conjugate vaccine yielded a safe and highly effective vaccine.
Topics: Africa South of the Sahara; Disease Transmission, Infectious; Humans; India; International Cooperation; Meningitis, Meningococcal; Meningococcal Vaccines; Neisseria meningitidis, Serogroup A; Technology, Pharmaceutical; World Health Organization
PubMed: 26553667
DOI: 10.1093/cid/civ595 -
Human Vaccines & Immunotherapeutics Feb 2017Neisseria meningitidis serogroup B (MenB) is an important cause of invasive meningococcal disease. The development of safe and effective vaccines with activity across... (Review)
Review
Neisseria meningitidis serogroup B (MenB) is an important cause of invasive meningococcal disease. The development of safe and effective vaccines with activity across the diversity of MenB strains has been challenging. While capsular polysaccharide conjugate vaccines have been highly successful in the prevention of disease due to meningococcal serogroups A, C, W, and Y, this approach has not been possible for MenB owing to the poor immunogenicity of the MenB capsular polysaccharide. Vaccines based on outer membrane vesicles have been successful in the prevention of invasive MenB disease caused by the single epidemic strain from which they were derived, but they do not confer broad protection against diverse MenB strains. Thus, alternative approaches to vaccine development have been pursued to identify vaccine antigens that can provide broad protection against the epidemiologic and antigenic diversity of invasive MenB strains. Human factor H binding protein (fHBP) was found to be such an antigen, as it is expressed on nearly all invasive disease strains of MenB and can induce bactericidal responses against diverse MenB strains. A bivalent vaccine (Trumenba®, MenB-FHbp, bivalent rLP2086) composed of equal amounts of 2 fHBP variants from each of the 2 immunologically diverse subfamilies of fHBP (subfamilies A and B) was the first MenB vaccine licensed in the United States under an accelerated approval pathway for prevention of invasive MenB disease. Due to the relatively low incidence of meningococcal disease, demonstration of vaccine efficacy for the purposes of licensure of bivalent rLP2086 was based on vaccine-elicited bactericidal activity as a surrogate marker of efficacy, as measured in vitro by the serum bactericidal assay using human complement. Because bacterial surface proteins such as fHBP are antigenically variable, an important component for evaluation and licensure of bivalent rLP2086 included stringent criteria for assessment of breadth of coverage across antigenically diverse and epidemiologically important MenB strains. This review describes the rigorous approach used to assess broad coverage of bivalent rLP2086. Alternative nonfunctional assays proposed for assessing vaccine coverage are also discussed.
Topics: Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Blood Bactericidal Activity; Cross Reactions; Drug Approval; Humans; Meningitis, Meningococcal; Meningococcal Vaccines; Neisseria meningitidis, Serogroup B; United States; Vaccines, Synthetic
PubMed: 27960595
DOI: 10.1080/21645515.2017.1264750