BACKGROUND: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination. METHODS: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe. In stage 1, healthy MenACWY vaccine-naive or -experienced 10- to 25-year-olds were randomized 1:2 to receive MenABCWY and placebo or MenB-fHbp and MenACWY-CRM. Eligible participants were randomly selected to participate in stage 2, which was an open-label immunopersistence and booster extension. Immunogenicity was assessed through serum bactericidal antibody using human complement (hSBA) assays with serogroups A/C/W/Y (MenA/C/W/Y) and 4 primary serogroup B (MenB) test strains. Immunogenicity endpoints included hSBA seroprotection rates through 48 months after primary vaccination and 1 month after the booster. Safety endpoints included booster reactogenicity events and adverse events (AEs). RESULTS: Of 1379 eligible participants, 353 entered stage 2; 242 completed the 48-month blood draw after primary vaccination and 240 completed the booster vaccination phase. MenA/C/W/Y seroprotection rates remained high for 4 years following a 2-dose MenABCWY primary series (MenACWY-naive, 62.0 %-100.0 %; MenACWY-experienced, 98.7 %-100.0 %) and trended higher than those after a single MenACWY-CRM dose (MenACWY-naive, 38.1 %-95.2 %; MenACWY-experienced, 89.7 %-100.0 %). Corresponding seroprotection rates against MenB remained stable and generally higher than baseline (MenABCWY, 18.2 %-36.6 %; MenB-fHbp, 16.2 %-31.9 % across strains). Following a booster, seroprotection rates against all 5 serogroups were ≥ 93.8 % across groups. Most booster dose reactogenicity events were mild or moderate in severity, and AEs were infrequent. CONCLUSIONS: Immune responses remained high for MenA/C/W/Y and above baseline for MenB through 4 years after the MenABCWY primary series, with robust responses for all 5 serogroups observed following a booster. The MenABCWY booster had an acceptable safety and tolerability profile consistent with the primary series. NCT03135834.
- MeSH
- dítě MeSH
- dospělí MeSH
- imunogenicita vakcíny MeSH
- komplement imunologie MeSH
- lidé MeSH
- meningokokové infekce * prevence a kontrola imunologie MeSH
- meningokokové vakcíny * imunologie škodlivé účinky aplikace a dávkování MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Neisseria meningitidis imunologie MeSH
- protilátky bakteriální * krev MeSH
- sekundární imunizace * metody MeSH
- séroskupina MeSH
- vakcíny konjugované imunologie aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Evropa MeSH
- Spojené státy americké MeSH
BACKGROUND: Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year. METHODS: From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). RESULTS: Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36-73). Adjusted VE was 48 % (95 %CI: 5-71) for dose one (416 eligible infants) and 76 % (95 %CI: 43-90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. CONCLUSIONS: Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three.
Influenza vaccination reduces the risk of adverse cardiovascular events.The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344).The primary endpoint wasthe composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. Thecumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion,there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccinationbut regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.
- MeSH
- chřipka lidská * prevence a kontrola komplikace MeSH
- infarkt myokardu * MeSH
- lidé MeSH
- trombóza * MeSH
- vakcinace metody MeSH
- vakcíny proti chřipce * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Tick-borne encephalitis (TBE) is a severe neuroinfection of humans. Dogs are also commonly infected with tick-borne encephalitis virus (TBEV). These infections are usually asymptomatic, but sometimes show clinical signs similar to those seen in humans and can be fatal. To date, there is no TBEV vaccine available for use in dogs. To address this need, a TBEV vaccine candidate for dogs based on inactivated whole virus antigen was developed. The safety, immunogenicity, and efficacy of the vaccine candidate were tested in mice as the preclinical model and in dogs as the target organism. The vaccine was well tolerated in both species and elicited the production of specific anti-TBEV antibodies with virus neutralising activity. Vaccination of mice provided complete protection against the development of fatal TBE. Immunisation of dogs prevented the development of viremia after challenge infection. Therefore, the developed vaccine candidate is promising to protect dogs from severe TBEV infections.
- MeSH
- imunizace MeSH
- klíšťová encefalitida * prevence a kontrola veterinární MeSH
- lidé MeSH
- myši MeSH
- protilátky virové MeSH
- psi MeSH
- vakcinace MeSH
- virové vakcíny * MeSH
- viry klíšťové encefalitidy * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The excessive covid-related mortality of psychiatric patients was reduced by vaccination. The vaccine uptake in patients diagnosed with different mental health disorders is, however, not fully described. AIMS: A nationwide, record-based retrospective cross-sectional study examines the effect of substance use, psychotic, affective, anxiety, and personality disorders on COVID-19 vaccination rates in August and December 2021. Further, it quantifies the effect of receiving mental healthcare on vaccine uptake. METHODS: The COVID-19 vaccine rates of mental healthcare users in August and December 2021 were examined using logistic regression models adjusted for sex and age on a sample of 7,235,690 adult inhabitants of the Czech Republic. The probability of vaccine uptake in the week following mental healthcare appointment or hospitalization on any day in the fall 2021 was compared to the general probability of getting vaccinated during that week. RESULTS: The vaccination rate in August 2021 was related to history of hospitalization due to substance use (OR = 0.71), personality (OR = 0.87), psychotic (OR = 0.92), and anxiety (OR = 1.15) disorders, while mood disorders had no effect (OR = 1.00). Compared to general population, mental healthcare users were undervaccinated in August but not in December 2021. Vaccine uptake was low in those with history of psychiatric hospitalizations but higher in those utilizing inpatient or outpatient mental healthcare recently, predominantly for affective disorders. Increased vaccine uptake was observed following utilization of mental healthcare as well as in those with repeated psychiatric hospitalizations. CONCLUSIONS: The vaccination rates of mental healthcare users relative to general population largely differ across nosological categories and during the vaccination campaign. Psychiatrists were successful in promoting vaccination against COVID-19.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- dospělí MeSH
- lidé MeSH
- průřezové studie MeSH
- retrospektivní studie MeSH
- služby péče o duševní zdraví * MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. METHODS: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. RESULTS: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. CONCLUSIONS: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.
BACKGROUND: Vaccination is the best mode of protection against tick-borne encephalitis (TBE) and its sequelae. The duration of protection and the optimal interval of repeat booster doses are still debated. The current study evaluated the persistence of the antibody response 11-15 years after a first booster vaccination following different primary vaccination schedules with a TBE vaccine (Encepur Adults, manufactured by Bavarian Nordic, previously by GSK). METHODS: This phase IV, open-label, mono-centric extension study enrolled adults who had received (at ≥ 12 years of age) primary vaccination with one of three randomly assigned TBE vaccine schedules (rapid [group R], conventional [group C], or accelerated conventional schedule [group A]) followed by a booster dose 3 years later. The antibody response was measured annually from 11 to 15 years post-booster using a TBE virus neutralization test (NT). An NT titer of ≥ 10 was considered as a clinically meaningful threshold and surrogate for protection. RESULTS: In total, 194 participants were enrolled and included in the per-protocol set; 188 completed the study. The percentage of participants with an NT titer ≥ 10 was 100% in group R and 99.0% in group A at all visits and ranged from 100% (year 11) to 95.8% (year 15) in group C. NT geometric mean titers were similar in the three study groups (181-267 in group R, 142-227 in group C, 141-209 in group A). NT geometric mean titers also remained high among participants ≥ 50 years old (98-206) and ≥ 60 years old (91-191) across study groups and time points. CONCLUSIONS: This study showed neutralizing antibody persistence for at least 15 years after a first booster dose of the Encepur Adults TBE vaccine in all age groups evaluated, regardless of which primary vaccination schedule was given to adolescents or adults. Trialregistry: ClinicalTrials.gov: NCT03294135.
- MeSH
- dospělí MeSH
- klíšťová encefalitida * prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- následné studie MeSH
- očkovací schéma MeSH
- předškolní dítě MeSH
- protilátky virové MeSH
- sekundární imunizace MeSH
- vakcinace MeSH
- virové vakcíny * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze IV MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
INTRODUCTION: Borrelia burgdorferi sensu lato, the causative agents of Lyme borreliosis, are transmitted by Ixodes ticks. Tick saliva proteins are instrumental for survival of both the vector and spirochete and have been investigated as targets for vaccine targeting the vector. In Europe, the main vector for Lyme borreliosis is Ixodes ricinus, which predominantly transmits Borrelia afzelii. We here investigated the differential production of I. ricinus tick saliva proteins in response to feeding and B. afzelii infection. METHOD: Label-free Quantitative Proteomics and Progenesis QI software was used to identify, compare, and select tick salivary gland proteins differentially produced during tick feeding and in response to B. afzelii infection. Tick saliva proteins were selected for validation, recombinantly expressed and used in both mouse and guinea pig vaccination and tick-challenge studies. RESULTS: We identified 870 I. ricinus proteins from which 68 were overrepresented upon 24-hours of feeding and B. afzelii infection. Selected tick proteins were successfully validated by confirming their expression at the RNA and native protein level in independent tick pools. When used in a recombinant vaccine formulation, these tick proteins significantly reduced the post-engorgement weights of I. ricinus nymphs in two experimental animal models. Despite the reduced ability of ticks to feed on vaccinated animals, we observed efficient transmission of B. afzelii to the murine host. CONCLUSION: Using quantitative proteomics, we identified differential protein production in I. ricinus salivary glands in response to B. afzelii infection and different feeding conditions. These results provide novel insights into the process of I. ricinus feeding and B. afzelii transmission and revealed novel candidates for an anti-tick vaccine.
- MeSH
- arachnida jako vektory MeSH
- klíště * MeSH
- lymeská nemoc * prevence a kontrola MeSH
- morčata MeSH
- myši MeSH
- proteiny členovců MeSH
- proteom MeSH
- slinné žlázy MeSH
- vakcíny * MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The MenB-FHbp vaccine is licensed to prevent meningococcal serogroup B disease on either a 2-dose (0, 6 months) or 3-dose (0, 1-2, 6 months) series. This phase 3 study further assessed the immunogenicity and safety of the 2-dose MenB-FHbp schedule. METHODS: Subjects 10-25 years of age received MenB-FHbp (months 0, 6) and the quadrivalent meningococcal conjugate vaccine MenACWY-CRM (month 0). Primary immunogenicity endpoints included percentages of subjects achieving ≥ 4-fold increases from baseline in serum bactericidal antibody using human complement (hSBA) titers for 4 diverse, vaccine-heterologous primary serogroup B test strains and titers ≥ lower limit of quantitation (LLOQ; 1:8 or 1:16) for all 4 primary strains combined (composite response) after dose 2; a titer ≥ 1:4 is the accepted correlate of protection. Percentages of participants with hSBA titers ≥ LLOQ for 10 additional vaccine-heterologous strains were also assessed; positive predictive values of primary strain responses for secondary strain responses were determined. Safety was assessed. RESULTS: Overall, 1057 subjects received dose 1 and 946 received dose 2 of MenB-FHbp. Percentages of participants achieving ≥ 4-fold increases in hSBA titers against each primary strain after dose 2 ranged from 67.4% to 95.0% and the composite response was 74.3%. Primary strain responses were highly predictive of secondary strain responses. Most reactogenicity events were mild-to-moderate in severity and did not lead to withdrawal from the study. Adverse events (AEs) considered by the investigator to be related to vaccination occurred in 4.2% (44/1057) of subjects, and there were no serious AEs or newly diagnosed chronic medical conditions considered related to vaccination. CONCLUSIONS: MenB-FHbp administered at 0, 6 months was well tolerated and induced protective bactericidal antibody responses against diverse serogroup B strains. Findings provide further support for the continued use of MenB-FHbp on a 2-dose schedule in this population.
- MeSH
- lidé MeSH
- meningokokové infekce * prevence a kontrola MeSH
- meningokokové vakcíny * škodlivé účinky MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Neisseria meningitidis séroskupiny B * MeSH
- Neisseria meningitidis * MeSH
- protilátky bakteriální MeSH
- séroskupina MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
Ixodes ricinus and Ixodes scapularis are the main vectors for the causative agents of Lyme borreliosis and a wide range of other pathogens. Repeated tick-bites are known to lead to tick rejection; a phenomenon designated as tick immunity. Tick immunity is mainly directed against tick salivary gland proteins (TSGPs) and has been shown to partially protect against experimental Lyme borreliosis. TSGPs recognized by antibodies from tick immune animals could therefore be interesting candidates for an anti-tick vaccine, which might also block pathogen transmission. To identify conserved Ixodes TSGPs that could serve as a universal anti-tick vaccine in both Europe and the US, a Yeast Surface Display containing salivary gland genes of nymphal I. ricinus expressed at 24, 48 and 72 h into tick feeding was probed with either sera from rabbits repeatedly exposed for 24 h to I. ricinus nymphal ticks and/or sera from rabbits immune to I. scapularis. Thus, we identified thirteen TSGP vaccine candidates, of which ten were secreted. For vaccination studies in rabbits, we selected six secreted TSGPs, five full length and one conserved peptide. None of these proteins hampered tick feeding. In contrast, vaccination of guinea pigs with four non-secreted TSGPs - two from the current and two from a previous human immunoscreening - did significantly reduce tick attachment and feeding. Therefore, non-secreted TSGPs appear to be involved in the development of tick immunity and are interesting candidates for an anti-tick vaccine.
