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Vaccine Jun 2024Meningococcal disease is caused by Neisseria meningitidis or meningococcus. Every year globally around 1.2 million people are affected and approximately 120,000 deaths...
Meningococcal disease is caused by Neisseria meningitidis or meningococcus. Every year globally around 1.2 million people are affected and approximately 120,000 deaths occur due to meningitis. The disease can be prevented by a single dose of meningococcal vaccine. We carried out a randomized observer-blinded non-inferiority trial to evaluate and compare the immunogenicity and safety of a local meningococcal polysaccharide vaccine 'Ingovax ACWY' (test) with Quadri Meningo (comparator), an approved meningococcal polysaccharide vaccine in India. A total of 88 healthy adults (18-45 years old) were randomized at a 1:1 ratio in two vaccine groups receiving a single dose vaccine subcutaneously. All participants were followed until three months post-vaccination. Blood for clinical parameters (hematology and biochemistry) and serum bactericidal assay (SBA) was collected prior to vaccination and one-month post-vaccination. Solicited adverse events (AEs) were assessed up to 6 days following vaccination and unsolicited AEs were monitored throughout the follow-up period. There was no significant difference in rates of AE between the two groups. The commonest solicited AE was injection site pain. No serious AEs were reported. There was no significant difference (p<0.05) in seroconversion rate as well as pre and post-vaccination SBA geometric mean titers (GMT)between test and comparator vaccine. The post-vaccination GMT ratio (GMR) of the test and comparator vaccine was found to be 0.9, 1, 1.29, and 0.85 for serogroup A, C, W135, and Y respectively. For all the serogroups, lower limit of 95% CI of the GMR was found to be greater than the pre-defined 0.5 non-inferiority margin suggesting that Ingovax ACWY is similar to Quadri Meningo vaccine. We observed the immunogenicity and safety of Ingovax ACWY is non-inferior to comparator vaccine. The development of facilities for manufacturing polysaccharide ACWY vaccines locally will further lead to capacity building in the field of vaccines for Bangladesh.
PubMed: 38897895
DOI: 10.1016/j.vaccine.2024.06.030 -
Healthcare (Basel, Switzerland) May 2024Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are...
BACKGROUND
Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are limited. This study aimed to investigate the in-depth experiences and impacts of IMD on AYAs.
METHODS
Participants were recruited from two Australian states, Victoria and South Australia. We conducted qualitative, semi-structured interviews with 30 patients diagnosed with IMD between 2016 and 2021. The interview transcripts were analyzed thematically.
RESULTS
Of the participants, 53% were aged 15-19 years old, and 47% were aged 20-24. The majority (70%) were female. Seven themes relating to the participants' experience of IMD were identified: (1) underestimation of the initial symptoms and then rapid escalation of symptoms; (2) reliance on social support for emergency care access; (3) the symptoms prompting seeking medical care varied, with some key symptoms missed; (4) challenges in early medical diagnosis; (5) traumatic and life-changing experience; (6) a lingering impact on HRQoL; and (7) gaps in the continuity of care post-discharge.
CONCLUSION
The themes raised by AYA IMD survivors identify multiple areas that can be addressed during their acute illness and recovery. Increasing awareness of meningococcal symptoms for AYAs may help reduce the time between the first symptoms and the first antibiotic dose, although this remains a challenging area for improvement. After the acute illness, conducting HRQoL assessments and providing multidisciplinary support will assist those who require more intensive and ongoing assistance during their recovery.
PubMed: 38891151
DOI: 10.3390/healthcare12111075 -
American Journal of Men's Health 2024Men aged 27 to 45 are eligible for human papillomavirus (HPV) vaccination as of 2019, yet relatively little is known about whether they have received or intend to...
Men aged 27 to 45 are eligible for human papillomavirus (HPV) vaccination as of 2019, yet relatively little is known about whether they have received or intend to receive it. We conducted a cross-sectional, online survey among fathers aged 27 to 45 between March and April 2022, to assess associations between HPV vaccination awareness, behaviors, intentions, and psychosocial constructs from the Health Belief Model. We examined the characteristics of those who had (a) heard of the HPV vaccine, (b) already received ≥ 1 dose, and (c) intentions for future vaccination among those who had never been vaccinated. Among 400 men who completed the survey, 32% were not aware of the HPV vaccine. Among those who were aware, 41% had received ≥ 1 dose. Sixty-three percent of unvaccinated men reported that they intended to get vaccinated in the future. Multivariable logistic regression analyses revealed that age and race/ethnicity were associated with having been vaccinated previously. Among the unvaccinated, multivariable logistic regression analyses revealed that those with a higher perceived risk of HPV-associated cancer had 3.73 greater odds of reporting they would seek vaccination compared to those with lower perceived risk (95% confidence interval [CI] = [1.28, 12.3]). We did not find perceived benefits, barriers, or decision self-efficacy to be related to future vaccine intentions. Since recommendations for this group include shared clinical decision-making, public health efforts should focus on raising awareness of vaccine eligibility, emphasizing risk factors for HPV-associated cancers so that individuals have an accurate perception of risk, and encouraging conversation between men and their providers.
Topics: Humans; Male; Papillomavirus Vaccines; Adult; Cross-Sectional Studies; Middle Aged; Fathers; Health Knowledge, Attitudes, Practice; Intention; Papillomavirus Infections; Surveys and Questionnaires; Vaccination
PubMed: 38879825
DOI: 10.1177/15579883241258823 -
Carbohydrate Polymers Oct 2024Meningococcal glycoconjugate vaccines sourced from capsular polysaccharides (CPSs) of pathogenic Neisseria meningitidis strains are well-established measures to prevent...
Meningococcal glycoconjugate vaccines sourced from capsular polysaccharides (CPSs) of pathogenic Neisseria meningitidis strains are well-established measures to prevent meningococcal disease. However, the exact structural factors responsible for antibody recognition are not known. CPSs of Neisseria meningitidis serogroups Y and W differ by a single stereochemical center, yet they evoke specific immune responses. Herein, we developed specific monoclonal antibodies (mAbs) targeting serogroups C, Y, and W and evaluated their ability to kill bacteria. We then used these mAbs to dissect structural elements responsible for carbohydrate-protein interactions. First, Men oligosaccharides were screened against the mAbs using ELISA to select putative lengths representing the minimal antigenic determinant. Next, molecular interaction features between the mAbs and serogroup-specific sugar fragments were elucidated using STD-NMR. Moreover, X-ray diffraction data with the anti-MenW CPS mAb enabled the elucidation of the sugar-antibody binding mode. Our findings revealed common traits in the epitopes of all three sialylated serogroups. The minimal binding epitopes typically comprise five to six repeating units. Moreover, the O-acetylation of the neuraminic acid moieties was fundamental for mAb binding. These insights hold promise for the rational design of optimized meningococcal oligosaccharides, opening new avenues for novel production methods, including chemical or enzymatic approaches.
Topics: Antibodies, Monoclonal; Serogroup; Neisseria meningitidis; Meningococcal Vaccines; Polysaccharides, Bacterial; Antibodies, Bacterial; Epitopes; Animals; Mice; Humans; Bacterial Capsules; Antibody Formation
PubMed: 38876728
DOI: 10.1016/j.carbpol.2024.122349 -
Arthritis Research & Therapy Jun 2024The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF‑06835375, a potent selective afucosyl immunoglobulin... (Randomized Controlled Trial)
Randomized Controlled Trial
A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis.
BACKGROUND
The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF‑06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
METHODS
This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18-70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03-6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3-10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects. Endpoints included treatment-emergent adverse events (TEAEs), pharmacokinetic parameters, pharmacodynamic effects on B and cTfh cells, and biomarker counts, vaccine response, and exploratory differential gene expression analysis. Safety, pharmacokinetic, and pharmacodynamic endpoints are summarized descriptively. The change from baseline of B and Tfh cell-specific genes over time was calculated using a prespecified mixed-effects model, with a false discovery rate < 0.05 considered statistically significant.
RESULTS
In total, 73 patients were treated (SAD cohorts: SLE, n = 17; RA, n = 14; MAD cohorts: SLE, n = 22; RA, n = 20). Mean age was 53.3 years. Sixty-two (84.9%) patients experienced TEAEs (placebo n = 17; PF-06835375 n = 45); most were mild or moderate. Three (9.7%) patients experienced serious adverse events. Mean t ranged from 3.4-121.4 h (SAD cohorts) and 162.0-234.0 h (MAD cohorts, Day 29). B and cTfh cell counts generally showed dose-dependent reductions across cohorts (range of mean maximum depletion: 67.3-99.3%/62.4-98.7% [SAD] and 91.1-99.6%/89.5-98.1% [MAD], respectively). B cell-related genes and pathways were significantly downregulated in patients treated with PF-06835375.
CONCLUSIONS
These data support further development of PF-06835375 to assess the clinical potential for B and Tfh cell depletion as a treatment for autoimmune diseases.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03334851.
Topics: Humans; Middle Aged; Adult; Double-Blind Method; Female; Male; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Aged; Receptors, CXCR5; Young Adult; Dose-Response Relationship, Drug; Adolescent; Antibodies, Monoclonal, Humanized; Antirheumatic Agents
PubMed: 38845046
DOI: 10.1186/s13075-024-03337-2 -
MMWR. Morbidity and Mortality Weekly... Jun 2024Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and...
Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).
Topics: Humans; Meningococcal Infections; United States; France; Saudi Arabia; Young Adult; Adult; Adolescent; Male; Female; Neisseria meningitidis; Child; Child, Preschool; United Kingdom; Middle Aged; Infant; Aged; Travel-Related Illness; Disease Outbreaks; Travel
PubMed: 38843099
DOI: 10.15585/mmwr.mm7322e1 -
Revista Paulista de Pediatria : Orgao... 2024To analyze the vaccination coverage and abandonment rates among children under two years old in Brazil, from 2015 to 2021.
OBJECTIVE
To analyze the vaccination coverage and abandonment rates among children under two years old in Brazil, from 2015 to 2021.
METHODS
A time-series ecological study. The dependent variables of the research were "vaccination coverage" and "abandonment rate", both assessed by Brazilian region. The data were extracted in July 2022 from the Information System of the National Immunization Program. The Prais-Winsten technique was used for the trend analysis, with the aid of the STATA 16.0 software.
RESULTS
The mean vaccination coverage in Brazil was 76.96%, with a decreasing trend during the period (Annual Percent Change=-5.12; confidence interval - CI95% -7.81; -2.34); in 2015, the rate was 88.85% and it dropped to 62.35% in 2021. In turn, the overall abandonment rate was 24.00% in 2015 and 9.01% in 2021, with a mean of 10.48% and a stationary trend (Annual Percentage Change=-9.54; CI95% -22.92; 6.12). In 2021, all the vaccines presented coverage values below 74.00% in the country.
CONCLUSIONS
The vaccination coverage rate trend among children under two years old was stationary or decreasing for all the immunobiologicals in all Brazilian regions, with the exception of yellow fever in the South and Southeast regions. There was an increase in the abandonment rate trend for the Meningococcal C vaccine in the country and, specifically in relation to the regions, for BCG in the North, Northeast, and Midwest and for Meningococcal C in the North and Northeast.
Topics: Humans; Brazil; Vaccination Coverage; Infant; Immunization Programs; Vaccination; Time Factors
PubMed: 38836806
DOI: 10.1590/1984-0462/2024/42/2023116 -
Frontiers in Cellular and Infection... 2024The genus , which colonizes mucosal surfaces, includes both commensal and pathogenic species that are exclusive to humans. The two pathogenic species are closely... (Review)
Review
The genus , which colonizes mucosal surfaces, includes both commensal and pathogenic species that are exclusive to humans. The two pathogenic species are closely related but cause quite different diseases, meningococcal sepsis and meningitis () and sexually transmitted gonorrhea ). Although obvious differences in bacterial niches and mechanisms for transmission exists, pathogenic have high levels of conservation at the levels of nucleotide sequences, gene content and synteny. Species of express broad-spectrum -linked protein glycosylation where the glycoproteins are largely transmembrane proteins or lipoproteins localized on the cell surface or in the periplasm. There are diverse functions among the identified glycoproteins, for example type IV biogenesis proteins, proteins involved in antimicrobial resistance, as well as surface proteins that have been suggested as vaccine candidates. The most abundant glycoprotein, PilE, is the major subunit of pili which are an important colonization factor. The glycans attached can vary extensively due to phase variation of protein glycosylation ( genes and polymorphic gene content. The exact roles of glycosylation in remains to be determined, but increasing evidence suggests that glycan variability can be a strategy to evade the human immune system. In addition, pathogenic and commensal appear to have significant glycosylation differences. Here, the current knowledge and implications of protein glycosylation genes, glycan diversity, glycoproteins and immunogenicity in pathogenic are summarized and discussed.
Topics: Humans; Bacterial Proteins; Glycoproteins; Glycosylation; Neisseria gonorrhoeae; Neisseria meningitidis; Polysaccharides; Meningitis, Meningococcal; Gonorrhea
PubMed: 38808060
DOI: 10.3389/fcimb.2024.1407863 -
Vaccine May 2024Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal...
INTRODUCTION
Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal but not pneumococcal meningitis. Mathematical modelling is a useful tool for assessing the potential impact of different pneumococcal control strategies. This work aimed to estimate the impact of reactive vaccination with pneumococcal conjugate vaccine (PCV) had it been implemented in past African meningitis belt outbreaks and assess their efficiency relative to existing routine infant immunisation with PCV.
METHODS & RESULTS
Using recent pneumococcal meningitis outbreaks in Burkina Faso, Chad, and Ghana as case studies, we investigated the potential impact of reactive vaccination. We calculated the number needed to vaccinate to avert one case (NNV) in each outbreak setting and over all outbreaks and compared this to the NNV for existing routine infant vaccination. We extended previous analyses of reactive vaccination by considering longer-term protection in vaccinees over five years, incorporating a proxy for indirect effects. We found that implementing reactive vaccination in previous pneumococcal meningitis outbreaks could have averted up to 10-20 % of outbreak cases, with the biggest potential impact in Brong Ahafo, Ghana (2015-2016) and Goundi, Chad (2009). The NNV, and hence the value of reactive vaccination, varied greatly. 'Large' (80 + cumulative modelled cases per 100,000 population) and/or 'prolonged' (exceeding a response threshold of 10 suspected cases per 100,000 per week for four weeks or more) outbreaks had NNV estimates under 10,000. For routine infant vaccination with PCV, the estimated NNV ranged from 3,100-5,600 in Burkina Faso and 1,500-2,600 in Ghana.
IMPLICATIONS
This analysis provides evidence to inform the design of pneumococcal meningitis outbreak response guidelines. Countries should consider reactive vaccination in each outbreak event, together with maintaining routine infant vaccination as the primary intervention to reduce pneumococcal disease burden and outbreak risk.
PubMed: 38797628
DOI: 10.1016/j.vaccine.2024.05.031 -
Vaccines Apr 2024The Banalia health zone in the Democratic Republic of Congo reported a meningitis epidemic in 2021 that evolved outside the epidemic season. We assessed the effects of...
BACKGROUND
The Banalia health zone in the Democratic Republic of Congo reported a meningitis epidemic in 2021 that evolved outside the epidemic season. We assessed the effects of the meningitis epidemic response.
METHODS
The standard case definition was used to identify cases. Care was provided to 2651 in-patients, with 8% of them laboratory tested, and reactive vaccination was conducted. To assess the effects of reactive vaccination and treatment with ceftriaxone, a statistical analysis was performed.
RESULTS
Overall, 2662 suspected cases of meningitis with 205 deaths were reported. The highest number of cases occurred in the 30-39 years age group (927; 38.5%). Ceftriaxone contributed to preventing deaths with a case fatality rate that decreased from 70.4% before to 7.7% after ceftriaxone was introduced ( = 0.001). W was isolated, accounting for 47/57 (82%), of which 92% of the strains belonged to the clonal complex 11. Reactive vaccination of individuals in Banalia aged 1-19 years with a meningococcal multivalent conjugate (ACWY) vaccine (Menactra) coverage of 104.6% resulted in an 82% decline in suspected meningitis cases (incidence rate ratio, 0.18; 95% confidence interval, 0.02-0.80; = 0.041).
CONCLUSION
Despite late detection (two months) and reactive vaccination four months after crossing the epidemic threshold, interventions implemented in Banalia contributed to the control of the epidemic.
PubMed: 38793712
DOI: 10.3390/vaccines12050461