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Vaccine Jul 2023Real-world studies on vaccine effects are diverse in terms of objectives, study setting and design, data type and scope, and analysis methods. In this review, we... (Review)
Review
BACKGROUND
Real-world studies on vaccine effects are diverse in terms of objectives, study setting and design, data type and scope, and analysis methods. In this review, we describe and discuss four-component meningococcal serogroup B vaccine (4CMenB vaccine, Bexsero) real-world studies with the aim of synthesizing their findings with application of standard methods.
METHODS
We performed a systematic literature review of all real-world studies on 4CMenB vaccine effects on meningococcal serogroup B disease, with no restriction for population age, vaccination schedule and/or type of vaccine effect evaluated (vaccine effectiveness [VE] and vaccine impact [VI] outcomes) published since its licensure in 2013 (from January 2014 until July 2021) in PubMed, Cochrane and the grey literature. We then aimed to synthesize the findings of the identified studies through application of standard synthesis methods.
RESULTS
According to reported criteria we retrieved five studies presenting estimates on 4CMenB vaccine effectiveness and impact. These studies showed great diversity in population, vaccination schedule and analysis methods mainly due to diversity in vaccine strategies and recommendations in the study settings. Directed by this diversity, no quantitative pooling methods to synthesize findings could be applied; instead we descriptively assessed study methods. We report VE estimates ranging from 59% to 94% and VI estimates ranging from 31% to 75%, representing diverse age groups, vaccination schedules and analysis methods.
CONCLUSION
Both vaccine outcomes showed real-life effectiveness of 4CMenB vaccine despite differences in study methodologies and vaccination strategies. Based on appraisal of study methods, we highlighted the need for an adapted tool which facilitates synthesis of heterogenic real-world vaccine studies when quantitative pooling methods are not applicable.
Topics: Humans; Infant; Meningococcal Vaccines; Meningococcal Infections; Serogroup; Neisseria meningitidis, Serogroup B
PubMed: 37321895
DOI: 10.1016/j.vaccine.2023.05.025 -
Human Vaccines & Immunotherapeutics Dec 2023This 2-stage Phase III study (NCT04142242) of a recently licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) assessed the safety and... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered as a booster to adults aged ≥59 years: A phase III randomized study.
This 2-stage Phase III study (NCT04142242) of a recently licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) assessed the safety and immunogenicity of a booster dose in older adults (≥59 years) primed with either MenACYW-TT or a quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immune persistence of MenACYW-TT and MPSV4 after primary vaccination was also evaluated. During Stage I, the participants administered MPSV4 (n = 165) or MenACYW-TT (n = 236) 3 years previously were randomized 9:2 to receive either a MenACYW-TT booster or to have blood drawn for persistence only. Participants primed with MPSV4 or MenACYW-TT 6-7 years previously had blood drawn for antibody persistence only. A serum bactericidal assay using human complement was used to measure functional antibodies against each serogroup at baseline and, for those receiving a booster, 30 days post-vaccination (D30). Proportions of participants with seroresponse (post-vaccination titers ≥1:16 when baseline titers <1:8 or ≥ 4-fold increase when baseline titers ≥1:8) were determined. Safety data were collected up to D30. Seroresponse rates for all serogroups at D30 ranged from 49.2% to 60.8% in the MPSV4-primed group, and 79.3-93.1% in the MenACYW-TT-primed group. MenACYW-TT induced sufficient seroresponses in each primed group. Geometric mean titers (GMTs) for serogroups C, W, and Y remained or trended higher than pre-vaccination levels at both 3 and 6-7 years after primary vaccination, indicating immune persistence. Safety outcomes were comparable between groups. A MenACYW-TT booster was immunogenic and well tolerated in participants aged ≥59 years regardless of previous quadrivalent meningococcal vaccine received. The greatest immune responses occurred in those primed with MenACYW-TT.
Topics: Aged; Humans; Antibodies, Bacterial; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Vaccination; Vaccines, Combined; Vaccines, Conjugate; Middle Aged
PubMed: 36632042
DOI: 10.1080/21645515.2022.2160600 -
FEBS Letters Aug 2020Factor H binding protein (fHbp) is a key virulence factor of Neisseria meningitidis and a main component of the two licensed vaccines against serogroup B meningococcus... (Review)
Review
Factor H binding protein (fHbp) is a key virulence factor of Neisseria meningitidis and a main component of the two licensed vaccines against serogroup B meningococcus (Bexsero and Trumenba). fHbp is a surface-exposed lipoprotein that enables the bacterium to survive in human blood by binding the human complement regulator factor H (fH). When used as vaccine, the protein induces antibodies with potent bactericidal activity. While the fHbp gene is present in the majority of N. meningitidis serogroup B isolates, the expression level varies up to 15 times between different strains and more than 700 different sequence variants have been described. Antigenically, the protein has been divided into three variants or two subfamilies. The 3D structure of fHbp alone, in combination with fH or in complex with bactericidal antibodies, has been key to understanding the molecular details of the protein. In this article, we will review the biochemical and immunological properties of fHbp, and its key role in meningococcal pathogenesis, complement regulation, and immune evasion.
Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Complement Factor H; Gene Expression Regulation, Bacterial; Humans; Immune Evasion; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis, Serogroup B; Protein Domains
PubMed: 32298465
DOI: 10.1002/1873-3468.13793 -
American Journal of Preventive Medicine Apr 2022A total of 3 vaccines are recommended for U.S. adolescents: tetanus, diphtheria, and acellular pertussis; meningococcal conjugate; and human papillomavirus. To...
INTRODUCTION
A total of 3 vaccines are recommended for U.S. adolescents: tetanus, diphtheria, and acellular pertussis; meningococcal conjugate; and human papillomavirus. To understand the disparities in vaccine availability and hesitancy, adolescent-, household-, and area-level characteristics associated with patterns of vaccine coverage are described.
METHODS
In 2020-2021, the authors generated national estimates among 8 possible combinations of vaccine coverage and identified the associated characteristics using 2015-2017 National Immunization Survey-Teen for male and female adolescents aged 13-17 years (N=63,299) linked to area (ZIP code) characteristics. Next, the factors associated with a missed opportunity for human papillomavirus vaccine (i.e., receipt of tetanus, diphtheria, and acellular pertussis and meningococcal conjugate only compared with coverage of all the 3 vaccines) were identified using logistic regression.
RESULTS
Most U.S. adolescents received all the 3 vaccines (42.9%) or tetanus, diphtheria, and acellular pertussis and meningococcal conjugate only (32.1%); fewer received no vaccines (7.7%) or tetanus, diphtheria, and acellular pertussis only (6.6%); and the remainder received some combination of 1-2 vaccines. Missed opportunities for human papillomavirus vaccination were more likely among adolescents who were male, were of White race, were uninsured, were in middle-income households, and were living in rural areas and were less likely among adolescents who were older, who were Medicaid insured, whose parents completed surveys in Spanish, who were in poverty-level households, and who were living in high-poverty areas.
CONCLUSIONS
A substantial number of U.S. adolescents are not fully vaccinated, and coverage varies by vaccine type, population, and place. Providers should routinely stock all the 3 vaccines and promote simultaneous, same-day vaccination to avoid missed vaccine opportunities. More research and interventions are needed to understand and modify patient, provider, payer, vaccine supply/storage, or other reasons for suboptimal coverage of all the recommended vaccines.
Topics: Adolescent; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Humans; Immunization Schedule; Male; Medically Uninsured; Meningococcal Vaccines; Papillomavirus Infections; Papillomavirus Vaccines; United States; Vaccination
PubMed: 35125272
DOI: 10.1016/j.amepre.2021.10.014 -
Vaccine Nov 2020Neisseria meningitidis, the causative agent of invasive meningococcal disease (IMD), is classified into different serogroups defined by their polysaccharide capsules.... (Review)
Review
Neisseria meningitidis, the causative agent of invasive meningococcal disease (IMD), is classified into different serogroups defined by their polysaccharide capsules. Meningococcal serogroups A, B, C, W, and Y are responsible for most IMD cases, with serogroup B (MenB) causing a substantial percentage of IMD cases in many regions. Vaccines using capsular polysaccharides conjugated to carrier proteins have been successfully developed for serogroups A, C, W, and Y. However, because the MenB capsular polysaccharide is poorly immunogenic, MenB vaccine development has focused on alternative antigens. The 2 currently available MenB vaccines (MenB-4C and MenB-FHbp) both include factor H binding protein (FHbp), a surface-exposed protein harboured by nearly all meningococcal isolates that is important for survival of the bacteria in human blood. MenB-4C contains a nonlipidated FHbp from subfamily B in addition to other antigens, including Neisserial Heparin Binding Antigen, Neisserial adhesin A, and outer membrane vesicles, whereas MenB-FHbp contains a lipidated FHbp from each subfamily (A and B). FHbp is highly immunogenic and a main target of bactericidal activity of antibodies elicited by both licensed MenB vaccines. FHbp is also an important vaccine component, in contrast to some other meningococcal antigens that may have limited cross-protection across strains, as FHbp-specific antibodies can provide broad cross-protection within each subfamily. Limited cross-protection between subfamilies necessitates the inclusion of FHbp variants from both subfamilies to achieve broad FHbp-based vaccine coverage. Additionally, immune responses to the lipidated form of FHbp have a superior cross-reactive profile to those elicited by the nonlipidated form. Taken together, the inclusion of lipidated FHbp variants from both FHbp subfamilies is expected to provide broad protection against the diverse disease-causing meningococcal strains expressing a wide range of FHbp sequence variants. This review describes the development of vaccines for MenB disease prevention, with a focus on the FHbp antigen.
Topics: Antigens, Bacterial; Bacterial Proteins; Carrier Proteins; Complement Factor H; Humans; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Neisseria meningitidis, Serogroup B
PubMed: 32878710
DOI: 10.1016/j.vaccine.2020.08.031 -
The Medical Letter on Drugs and... Mar 2024
Topics: Humans; Meningococcal Vaccines; Vaccines, Combined; Bacterial Vaccines
PubMed: 38466212
DOI: 10.58347/tml.2024.1698b -
Postgraduate Medicine Nov 2019: Adolescents and young adults are the primary reservoirs and transmitters of meningococci. In the US, meningococcal serogroup B (MenB) disease predominates over A, C,...
: Adolescents and young adults are the primary reservoirs and transmitters of meningococci. In the US, meningococcal serogroup B (MenB) disease predominates over A, C, W, and Y; ACIP-recommended MenACWY and MenB vaccines are available. We investigated invasive meningococcal disease (IMD) burden and vaccination among non-college adolescents.: IMD incidence by college attendance status and vaccination rates were analyzed using publicly available surveillance data.: 64/158 IMD cases occurred in non-college 18-24-year-olds during 2015-2017. Among non-college cases, the MenACWY vaccination rates were 38%-57% vs 90%-100% among college cases when vaccination status was known; MenB vaccination was 0% vs 0%-7%, respectively. In 2018, 17.2% of all 17-year-olds received ≥1 dose of multidose MenB vaccines; ≤50% completed the series.: Meningococcal vaccination is emphasized for college-bound adolescents, but non-college adolescents bear much of the disease burden. Low vaccine receipt preserves their risk, underscoring the need to protect all adolescents through vaccination.
Topics: Adolescent; Decision Making; Female; Humans; Male; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Patient Participation; Practice Patterns, Physicians'; United States; Vaccination Coverage; Young Adult
PubMed: 31575310
DOI: 10.1080/00325481.2019.1671667 -
Journal of Clinical Pharmacy and... Apr 2020This review describes invasive meningococcal disease (IMD) epidemiology in the United States, provides a brief overview of available meningococcal vaccines and discusses... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
This review describes invasive meningococcal disease (IMD) epidemiology in the United States, provides a brief overview of available meningococcal vaccines and discusses meningococcal serogroup B (MenB) vaccine development. Particular focus is given to the recombinant protein MenB vaccine, MenB-FHbp (Trumenba , bivalent rLP2086) in light of recent publication of phase 3 data; the other MenB vaccine (Bexsero , MenB-4C) has been recently reviewed. Current recommendations of the US Advisory Committee on Immunization Practices (ACIP) for MenB vaccination and potential barriers to immunization are also discussed.
METHODS
Using the published literature, this article reviews the development and use of MenB-FHbp to date, with a focus on the United States.
RESULTS AND DISCUSSION
Despite the availability of medical treatment, IMD is associated with significant mortality and frequently occurring serious permanent sequelae in surviving individuals. Worldwide, most IMD is caused by six serogroups (A, B, C, W, X and Y). MenB is the most common disease-causing meningococcal serogroup in the United States and has caused several recent university-based IMD outbreaks. MenB vaccines, including MenB-FHbp, are available in the United States. ACIP recommends that all individuals ≥10 years of age at increased risk for meningococcal disease receive MenB vaccination; healthy individuals 16-23 years of age are recommended MenB vaccines based on individual clinical decision-making. MenB-FHbp is used on a 2-dose schedule (0, 6 months) when vaccinating healthy individuals and on a tailored 3-dose schedule (0, 1-2, 6 months) in cases of increased risk.
WHAT IS NEW AND CONCLUSION
Because vaccination provides the most effective protection against IMD, pharmacists are in an excellent position to offer evidence-based vaccine information, as well as to encourage and provide meningococcal immunizations to adolescents and young adults.
Topics: Adolescent; Child; Humans; Immunization Schedule; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis, Serogroup B; Pharmacists; Professional Role; United States; Vaccination; Young Adult
PubMed: 31820483
DOI: 10.1111/jcpt.13083 -
BMC Public Health May 2023Men who have sex with men (MSM) have suboptimal uptake of human papillomavirus (HPV) and meningococcal vaccines. This study examines barriers and facilitators to HPV and...
BACKGROUND
Men who have sex with men (MSM) have suboptimal uptake of human papillomavirus (HPV) and meningococcal vaccines. This study examines barriers and facilitators to HPV and meningococcal vaccination among MSM in a large, racially/ethnically diverse, and medically underserved U.S. region.
METHODS
In 2020, we conducted five focus groups with MSM living in the Inland Empire, California. Participants discussed (1) their knowledge about and attitudes toward HPV, meningococcal disease, and related vaccines; and (2) factors that would encourage or discourage vaccine uptake. Data were systematically analyzed to identify salient barriers and facilitators to vaccination.
RESULTS
Participants (N = 25) had a median age of 29. Most were Hispanic (68%), self-identified as gay (84%), and had college degrees (64%). Key barriers to vaccination included: (1) limited awareness and knowledge about HPV and meningococcal disease, (2) reliance on mainstream healthcare providers for vaccine information, (3) stigma and reluctance to disclose sexual orientation, (4) uncertainty about health insurance coverage and vaccine costs, and (5) distance and time required to access vaccines. Key facilitators to vaccination were: (1) vaccine confidence, (2) perceived severity of HPV and meningococcal disease, (3) bundling vaccination into routine healthcare, and (4) pharmacies as vaccination sites.
CONCLUSIONS
Findings highlight opportunities for HPV and meningococcal vaccine promotion, including targeted education and awareness campaigns for MSM, LGBT inclusivity training for healthcare providers, and structural interventions to improve vaccine accessibility.
Topics: Humans; Male; Homosexuality, Male; Meningococcal Vaccines; Papillomavirus Infections; Human Papillomavirus Viruses; Focus Groups; Qualitative Research; Health Knowledge, Attitudes, Practice; Social Stigma; Health Services Accessibility; United States; Adult; Middle Aged; Insurance, Health
PubMed: 37221575
DOI: 10.1186/s12889-023-15847-w -
Human Vaccines & Immunotherapeutics Dec 2023Invasive meningococcal disease (IMD) is rare but associated with high morbidity and mortality. In the United States, the most vulnerable age groups are infants and... (Review)
Review
Serum bactericidal activity against circulating and reference strains of meningococcal serogroup B in the United States: A review of the strain coverage of meningococcal serogroup B (MenB) vaccines in adolescents and young adults.
Invasive meningococcal disease (IMD) is rare but associated with high morbidity and mortality. In the United States, the most vulnerable age groups are infants and adolescents/young adults, and the most common type of IMD is caused by serogroup B (MenB). MenB is preventable among adolescents and young adults with the use of two licensed vaccines, MenB-FHbp (Trumenba®, bivalent rLP2086; Pfizer Inc, Collegeville, PA) and MenB-4C (Bexsero®; GSK Vaccines, Srl, Italy). Because the effectiveness of MenB vaccination is dependent on broad vaccine coverage across circulating disease-causing strains, we reviewed the available clinical and real-world evidence regarding breadth of coverage of the two licensed vaccines in adolescents and young adults in the United States. Both vaccines protect against various MenB strains. More controlled data regarding breadth of coverage across MenB strains are available for MenB-FHbp compared with MenB-4C, whereas more observational data regarding US outbreak strain susceptibility are available for MenB-4C.
Topics: Adolescent; Young Adult; Humans; United States; Serogroup; Meningococcal Infections; Meningococcal Vaccines; Vaccination; Neisseria meningitidis, Serogroup B; Italy; Antigens, Bacterial
PubMed: 37257838
DOI: 10.1080/21645515.2023.2212570