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The Journal of Infectious Diseases Apr 2024Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with one dose being two-thirds as protective as two. We...
BACKGROUND
Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with one dose being two-thirds as protective as two. We examined the cost-effectiveness of vaccinating men-who-have-sex-with-men (MSM) in England, with one- or two-dose primary vaccination.
METHODS
Integrated transmission-dynamic health-economic modeling explored the effects of targeting strategy, first- and second-dose uptake levels, and duration of vaccine protection, using observational estimates of vaccine protection.
RESULTS
Vaccination with one or two primary doses is always cost-saving, irrespective of uptake, although vaccine sentiment is an important determinant of impact and cost-effectiveness. The most impactful and cost-effective targeting is offering "Vaccination-according-to-Risk" (VaR), to all patients with gonorrhea plus those reporting high numbers of sexual partners. If VaR is not feasible to implement then the more-restrictive strategy of "Vaccination-on-Diagnosis" (VoD) with gonorrhea is cost-effective, but much less impactful. Under conservative assumptions, VaR(2-dose) saves £7.62M(95%CrI:1.15-17.52) and gains 81.41(28.67-164.23) QALYs over 10 years; VoD(2-dose) saves £3.40M(0.48-7.71) and gains 41.26(17.52-78.25) QALYs versus no vaccination. Optimistic versus pessimistic vaccine-sentiment assumptions increase net benefits by ∼30%(VoD) or ∼60%(VaR).
CONCLUSIONS
At UK costs, targeted 4CMenB vaccination of MSM gains QALYs and is cost-saving at any uptake level. Promoting uptake maximizes benefits and is an important role for behavioral science.
PubMed: 38630583
DOI: 10.1093/infdis/jiae123 -
BMJ Open Apr 2024Gonorrhoea, the sexually transmissible infection caused by , has a substantial impact on sexual and reproductive health globally with an estimated 82 million new...
Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against infection in men who have sex with men: the GoGoVax study protocol.
INTRODUCTION
Gonorrhoea, the sexually transmissible infection caused by , has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by , may provide cross-protection against the closely related bacterium . This study will evaluate the efficacy of 4CMenB against infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+).
METHODS AND ANALYSIS
This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of -specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by genotype and antimicrobial resistance phenotype, and level and functional activity of -specific antibodies.
ETHICS AND DISSEMINATION
Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences.
TRIAL REGISTRATION NUMBER
NCT04415424.
Topics: Male; Humans; Gonorrhea; Meningococcal Vaccines; Meningococcal Infections; Homosexuality, Male; Sexual and Gender Minorities; Neisseria gonorrhoeae; Anti-Infective Agents; HIV Infections; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38626958
DOI: 10.1136/bmjopen-2023-081675 -
ImmunoHorizons Apr 2024Activation of the adaptive immune system requires the engagement of costimulatory pathways in addition to B and T cell Ag receptor signaling, and adjuvants play a...
Activation of the adaptive immune system requires the engagement of costimulatory pathways in addition to B and T cell Ag receptor signaling, and adjuvants play a central role in this process. Many Gram-negative bacterial polysaccharide vaccines, including the tetravalent meningococcal conjugate vaccines (MCV4) and typhoid Vi polysaccharide vaccines, do not incorporate adjuvants. The immunogenicity of typhoid vaccines is due to the presence of associated TLR4 ligands in these vaccines. Because the immunogenicity of MCV4 is poor and requires boosters, I hypothesized that TLR4 ligands are absent in MCV4 and that incorporation of a TLR4 ligand-based adjuvant would improve their immunogenicity. Consistent with this hypothesis, two Food and Drug Administration-approved MCV4 vaccines, MENVEO and MenQuadfi, lack TLR4 ligands. Admixing monophosphoryl lipid A, a TLR4 ligand-based adjuvant formulation named "Turbo" with MCV4 induced significantly improved IgM and IgG responses to all four meningococcal serogroup polysaccharides in adult and aged mice after a single immunization. Furthermore, in infant mice, a single booster was sufficient to promote a robust IgG response and 100% seroconversion when MCV4 was adjuvanted with Turbo. Turbo upregulated the expression of the costimulatory molecules CD40 and CD86 on B cells, and Turbo-driven adjuvanticity is lost in mice deficient in CD40 and CD86. These data suggest that Turbo induces the required costimulatory molecules for its adjuvant activity and that incorporation of Turbo could make bacterial polysaccharide vaccines more immunogenic, minimize booster requirements, and be cost-effective, particularly for those individuals in low- and middle-income and disease-endemic countries.
Topics: Humans; United States; Adult; Infant; Animals; Mice; Vaccines, Combined; Ligands; Toll-Like Receptor 4; Adjuvants, Immunologic; Lipid A; Immunoglobulin G
PubMed: 38625118
DOI: 10.4049/immunohorizons.2400013 -
EClinicalMedicine May 2024The Sanofi/GSK AS03-adjuvanted (VidPrevtyn Beta) vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine were offered to adults aged 75...
BACKGROUND
The Sanofi/GSK AS03-adjuvanted (VidPrevtyn Beta) vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine were offered to adults aged 75 years and over in England from 3rd April 2023. This is the first time an adjuvanted COVID-19 vaccine has been administered as part of a UK COVID-19 vaccination programme. In clinical trials, antibody levels generated were comparable with mRNA vaccines but there are no real-world data on the effectiveness or duration of protection.
METHODS
We used a test-negative case-control study design to estimate the incremental vaccine effectiveness of the Sanofi/GSK and Pfizer bivalent BA.4-5 boosters against hospitalisation amongst those aged 75 years and older in England. Cases (those testing positive) and controls (those testing negative) were identified from the national COVID-19 PCR testing data undertaken in hospital settings. The study period included tests from 3rd April 2023 to 27th August 2023. Tests were linked to the COVID-19 vaccination register and to the national hospital admission database, restricting to those with an acute respiratory infection coded in the primary diagnosis field. Vaccine effectiveness was estimated using multivariable logistic regression amongst those who had last received an autumn 2022 booster given at least 3 months prior. The test result was the outcome and vaccination status the exposure. Analyses were adjusted for week of test, gender, age, clinical risk group status, care home resident status, region, index of multiple deprivation, ethnicity, influenza vaccination status and recent COVID-19 positivity.
FINDINGS
There were 14,169 eligible tests from hospitalised individuals aged 75 years and older; 3005 cases (positive tests) and 11,164 controls (negative tests). Effectiveness was highest in the period 9-13 days post vaccination for both manufacturers at about 50%; 43.7% (95% CI, 20.1-60.3%) and 56.1% (95% CI, 25.2-74.2%) for Sanofi/GSK and Pfizer BA.4-5, respectively. There was evidence of waning with a reduction to about 30% for both manufacturers after 5-9 weeks. The longest time interval post vaccination for which we were able to estimate effectiveness was 10+ weeks post vaccination, at which point vaccine effectiveness was 17.6% (95% CI, -3.6 to 34.5%) and 37.9% (95% CI, 13.2-55.5%) for the Sanofi/GSK and Pfizer BA.4-5 boosters, respectively.
INTERPRETATION
Both boosters provided good protection against hospitalisation amongst older adults. The finding that the adjuvanted vaccine targeting the distant Beta strain had similar effectiveness to the bivalent mRNA vaccine targeting more closely matched Omicron sub-lineages is notable and highlights the need for further real-world studies into the effectiveness of vaccines from different vaccine platforms and formulations in the presence of matched and unmatched strains.
FUNDING
No external funding.
PubMed: 38618208
DOI: 10.1016/j.eclinm.2024.102587 -
Vaccine Nov 2023Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to... (Observational Study)
Observational Study
AIMS
Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to estimate vaccination coverage and timeliness in Swiss children over a decade. Furthermore, we evaluated the impact of COVID-19, regional variations, and the adherence to the amended vaccination schedule in 2019.
METHODS
Retrospective observational study with Swiss health insurance claims data including birth cohorts 2012-2021 of children continuously observed until ages 13, 25, and 48 months respectively. We used population-weighted proportions and time-to-event analyses to describe coverage and timeliness of diphtheria/tetanus/pertussis/poliomyelitis/haemophilus influenzae type b (DTaP-IPV-Hib), measles/mumps/rubella (MMR), hepatitis B (HBV), pneumococcal (PCV), and meningococcal (MCV) vaccinations according to the national schedule. The potential impact of COVID-19 and vaccination schedule adherence were evaluated descriptively. Logistic regression was used to investigate regional factors potentially associated with non-vaccination.
RESULTS
120,073 children, representing between 12 and 17 % of all Swiss children born in corresponding years, were included. Coverage remained stable or improved over the years. The 2019 amendment of the national immunization schedule was associated with an increase of ~10 % points in full coverage in Swiss children for DTaP-IPV-Hib, MMR and HBV despite the concurrent COVID-19 pandemic. Nonetheless, full vaccination coverage remained below 90 % with many vaccination series being delayed or not completed. The comparison across the different vaccines revealed large differences in coverage. Moreover, we observed large regional differences in non-vaccination with children living in rural and German-speaking areas more likely to be entirely unvaccinated.
CONCLUSION
Full vaccination coverage in Swiss children is still below 90 % with many vaccinations administered delayed. Given regional differences, missed or delayed booster vaccinations, and differences in vaccine-specific acceptability, more effort may be needed to achieve national vaccination targets.
Topics: Child; Humans; Infant; Vaccination Coverage; Birth Cohort; Pandemics; Switzerland; Diphtheria-Tetanus-Pertussis Vaccine; Vaccination; Rubella Vaccine; Immunization Schedule; Haemophilus Vaccines; COVID-19
PubMed: 38593195
DOI: 10.1016/j.vaccine.2023.10.043 -
Anales de Pediatria May 2024
Topics: Humans; Meningococcal Infections; Meningococcal Vaccines; Child; Healthcare Disparities
PubMed: 38582645
DOI: 10.1016/j.anpede.2024.03.023 -
Journal of Behavioral Medicine Jun 2024Awareness and uptake of the meningitis vaccine remains low among marginalized groups, such as Latino men who have sex with men (LMSM), potentially due to structural and...
Awareness and uptake of the meningitis vaccine remains low among marginalized groups, such as Latino men who have sex with men (LMSM), potentially due to structural and psychosocial barriers in accessing preventative healthcare. The current study explored awareness and uptake of meningitis vaccines among a group of LMSM (N = 99) living in South Florida. A three-pronged variable selection approach was utilized prior to conducting regression models (linear and logistic). Overall, 48.5% of the participants reported little to no knowledge about meningitis vaccines, and 20.2% reported being vaccinated. Living with HIV (OR = 10.48) and time since outbreak (OR = 1.03) were significant predictors of meningitis vaccine uptake. No significant correlates of meningitis vaccine awareness were identified. More research is needed to identify other important factors associated with meningitis vaccine awareness and uptake among LMSM, a multiple marginalized group.
Topics: Humans; Male; Disease Outbreaks; Florida; Health Knowledge, Attitudes, Practice; Hispanic or Latino; Homosexuality, Male; Meningitis; Vaccination; Meningococcal Vaccines
PubMed: 38581595
DOI: 10.1007/s10865-024-00486-2 -
The Medical Letter on Drugs and... Apr 2024
Topics: Humans; Myasthenia Gravis; Immunosuppressive Agents; Complement C5; Peptides, Cyclic
PubMed: 38576149
DOI: 10.58347/tml.2024.1700c -
Modelling the Public Health Impact of MenACWY and MenC Adolescent Vaccination Strategies in Germany.Infectious Diseases and Therapy Apr 2024Invasive meningococcal disease (IMD) causes significant mortality and long-term sequelae. This study assesses the potential public health impact of adolescent...
INTRODUCTION
Invasive meningococcal disease (IMD) causes significant mortality and long-term sequelae. This study assesses the potential public health impact of adolescent vaccination strategies employing MenACWY and MenC vaccines in Germany, where the existing meningococcal immunisation programme predominantly involves MenC administration in toddlers.
METHODS
A dynamic transmission model was developed to simulate the carriage of five meningococcal serogroup compartments (AY/B/C/W/Other) from 2019 until 2060 within 1-year age groups from 0 to 99 years of age. IMD cases were estimated based on case-carrier ratios. The model considered vaccine effectiveness against carriage acquisition and IMD.
RESULTS
The model predicts that introducing MenACWY adolescent vaccination could lead to a considerable reduction in IMD incidence, with the potential to prevent up to 65 cases per year and a cumulative total of 1467 cases by 2060. This decrease, mainly driven by herd effects, would result in a reduction of IMD incidence across all age groups, regardless of vaccination age. Furthermore, implementing MenACWY vaccination in adolescents is projected to decrease annual MenACWY-related IMD mortality by up to 64%, equating to an overall prevention of 156 IMD deaths by 2060. These protective outcomes are expected to culminate in approximately 2250 life years gained (LYG) throughout the model's projected time horizon. In contrast, the adoption of MenC vaccination in adolescents is predicted to have minimal influence on both IMD incidence and mortality, as well as on LYG.
CONCLUSION
The results of this study demonstrate that implementing MenACWY vaccination for adolescents in Germany is likely to notably reduce IMD incidence and mortality across age groups. However, the introduction of MenC adolescent vaccination shows only limited impact. Considering the extensive healthcare resources typically required for IMD management, these findings suggest the potential for economic benefits associated with the adoption of MenACWY adolescent vaccination, warranting further cost-effectiveness analysis.
PubMed: 38570446
DOI: 10.1007/s40121-024-00958-7 -
Human Vaccines & Immunotherapeutics Dec 2024Vaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023... (Review)
Review
Vaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023 included recommendations for co-administration of pediatric vaccines, including the four-component vaccine for meningococcus B (4CMenB), pneumococcal conjugate vaccine (PCV), hexavalent vaccines, and oral rotavirus vaccines. Safety is a major concern when considering vaccine co-administration; therefore, a literature review of the available evidence on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines was performed. Of 763 publications screened, two studies were reviewed that reported safety data on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines in infants aged 0-24 months. Overall, these studies supported that there were no significant safety signals when co-administering 4CMenB with PCV, hexavalent/pentavalent, and rotavirus vaccines, compared with individual vaccination. This review provides key insights for healthcare professionals on the tolerability of co-administering 4CMenB with routine vaccines.
Topics: Humans; Infant; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis, Serogroup B; Rotavirus Vaccines; Vaccination; Vaccines, Conjugate; Infant, Newborn; Pneumococcal Vaccines
PubMed: 38566502
DOI: 10.1080/21645515.2024.2333106