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
- MeSH
- Borrelia burgdorferi komplex klasifikace patogenita MeSH
- ceftriaxon farmakologie terapeutické užití MeSH
- dítě MeSH
- doxycyklin farmakologie terapeutické užití MeSH
- erythema chronicum migrans diagnóza etiologie klasifikace MeSH
- lidé MeSH
- lymeská nemoc * diagnóza farmakoterapie komplikace prevence a kontrola MeSH
- lymská neuroborelióza diagnóza komplikace mikrobiologie MeSH
- protilátky bakteriální analýza klasifikace MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Meningococcal serogroups A, B, C, W, and Y cause nearly all meningococcal disease, and comprehensive protection requires vaccination against all five serogroups. We aimed to assess the immunogenicity and safety of a pentavalent MenABCWY vaccine comprising two licensed vaccines-meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) and a quadrivalent meningococcal serogroup ACWY tetanus toxoid conjugate vaccine (MenACWY-TT)-compared with two doses of MenB-FHbp and a single dose of quadrivalent meningococcal serogroup ACWY CRM197-conjugate vaccine (MenACWY-CRM) as the active control. We previously reported the primary safety and immunogenicity data relating to the two-dose MenB-FHbp schedule. Here we report secondary outcomes and ad-hoc analyses relating to MenABCWY immunogenicity and safety. METHODS: We did an observer-blind, active-controlled trial at 68 sites in the USA, Czech Republic, Finland, and Poland. Healthy individuals (aged 10-25 years) who had or had not previously received a MenACWY vaccine were randomly assigned (1:2) using an interactive voice or web-based response system, stratified by previous receipt of a MenACWY vaccine, to receive 0·5 mL of MenABCWY (months 0 and 6) and placebo (month 0) or MenB-FHbp (months 0 and 6) and MenACWY-CRM (month 0) via intramuscular injection into the upper deltoid. All individuals were masked to group allocation, except staff involved in vaccine dispensation, preparation, and administration; and protocol adherence. Endpoints for serogroups A, C, W, and Y included the proportion of participants who achieved at least a four-fold increase in serum bactericidal antibody using human complement (hSBA) titres between baseline and 1 month after each vaccination. For serogroup B, secondary endpoints included the proportion of participants who achieved at least a four-fold increase in hSBA titres from baseline for each of four primary test strains and the proportion of participants who achieved titres of at least the lower limit of quantitation against all four test strains combined at 1 month after the second dose. Endpoints for serogroups A, C, W, and Y were assessed in the modified intent-to-treat (mITT) population, which included all randomly assigned participants who received at least one vaccine dose and had at least one valid and determinate MenB or serogroup A, C, W, or Y assay result before vaccination up to 1 month after the second dose, assessed in ACWY-experienced and ACWY-naive participants separately. Secondary endpoints for serogroup B were analysed in the evaluable immunogenicity population, which included all participants in the mITT population who were randomly assigned to the group of interest, received all investigational products as randomly assigned, had blood drawn for assay testing within the required time frames, had at least one valid and determinate MenB assay result after the second vaccination, and had no important protocol deviations; outcomes were assessed in both ACWY-experienced and ACWY-naive populations combined. Non-inferiority of MenABCWY to MenACWY-CRM and MenB-FHbp was determined using a -10% non-inferiority margin for these endpoints. Reactogenicity and adverse events were assessed among all participants who received at least one vaccine dose and who had available safety data. This trial is registered with Clinicaltrials.gov, NCT03135834, and is complete. FINDINGS: Between April 24 and November 10, 2017, 1610 participants (809 MenACWY-naive; 801 MenACWY-experienced) were randomly assigned: 544 to receive MenABCWY and placebo (n=272 MenACWY-naive; n=272 MenACWY-experienced) and 1066 to receive MenB-FHbp and MenACWY-CRM (n=537 MenACWY-naive; n=529 MenACWY-experienced). Among MenACWY-naive or MenACWY-experienced MenABCWY recipients, 75·5% (95% CI 69·8-80·6; 194 of 257; serogroup C) to 96·9% (94·1-98·7; 254 of 262; serogroup A) and 93·0% (88·4-96·2; 174 of 187; serogroup Y) to 97·4% (94·4-99·0; 224 of 230; serogroup W) achieved at least four-fold increases in hSBA titres against serogroups ACWY after dose 1 or 2, respectively, in ad-hoc analyses. Additionally, 75·8% (71·5-79·8; 320 of 422) to 94·7% (92·1-96·7; 396 of 418) of MenABCWY and 67·4% (64·1-70·6; 563 of 835) to 95·0% (93·3-96·4; 782 of 823) of MenB-FHbp recipients achieved at least four-fold increases in hSBA titres against MenB strains after dose 2 in secondary analyses; 79·9% (334 of 418; 75·7-83·6) and 74·3% (71·2-77·3; 605 of 814), respectively, achieved composite responses. MenABCWY was non-inferior to MenACWY-CRM (single dose) and to MenB-FHbp in ad-hoc analyses based on the proportion of participants with at least a four-fold increase in hSBA titres from baseline and (for MenB-FHbp only) composite responses. Reactogenicity events after vaccination were similarly frequent across groups, were mostly mild or moderate, and were unaffected by MenACWY experience. No adverse events causing withdrawals were related to the investigational product. Serious adverse events were reported in four (1·5%; 0·4-3·7) MenACWY-naive individuals in the MenABCWY group versus six (2·2%; 0·8-4·8) among MenACWY-experienced individuals in the MenABCWY group and 14 (1·3%; 0·7-2·2) in the active control group (MenACWY-experienced and MenACWY-naive individuals combined); none of these were considered related to the investigational product. INTERPRETATION: MenABCWY immune responses were robust and non-inferior to MenACWY-CRM and MenB-FHbp administered separately, and MenABCWY was well tolerated. The favourable benefit-risk profile supports further MenABCWY evaluation as a simplified schedule compared with current adolescent meningococcal vaccination programmes. FUNDING: Pfizer.
- MeSH
- imunogenicita vakcíny MeSH
- kombinované vakcíny MeSH
- lidé MeSH
- meningokokové infekce * prevence a kontrola farmakoterapie MeSH
- meningokokové vakcíny * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Neisseria meningitidis séroskupiny B * MeSH
- Neisseria meningitidis * MeSH
- protilátky bakteriální MeSH
- vakcinace metody MeSH
- vakcíny konjugované MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie 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
OBJECTIVES: Lyme borreliosis is a tick-borne disease of increasing incidence and public concern. Our cross-sectional study was aimed at evaluating seroprevalence of Borrelia burgdorferi in a group of respondents from Eastern Slovakia. METHODS: In total, 515 blood samples collected in 2013-2016 were analysed with NovaLisaTM, NovaTec - Borrelia IgG/IgM kit (Immunodiagnostica, Dietzenbach, Germany). Positive and equivocal IgG-antibody results were further examined with immunoblotting (LYMECHECK® OPTIMA IgG and IgM kits, BIOSYNEX, France). Data detected by serological methods were matched with those obtained from a questionnaire. Differences between groups by residence/seropositivity were tested by χ2 test. The effect of socio-demographic and risk factors on seropositivity of IgG antibodies was assessed using binary logistic regression. RESULTS: IgG antibodies against Borrelia burgdorferi were detected in 67 cases (13.01%) and IgM antibodies in 40 cases (7.8%). Previous tick bite had been noted in 67.2% of these seropositive individuals. Higher seropositivity was observed in men and persons aged over 61 years. Rural residents had higher seropositivity (39%) than those living in urban (29%) areas. Very few of these seropositive persons reported prior symptoms. CONCLUSION: The study reveals that IgG-seropositivity for Borrelia burgdorferi in Eastern Slovakia is predominant in men and occurs mainly in rural areas. The findings also suggest that exposure to Borrelia burgdorferi (with subsequent antibody response in serum) does occur, mostly without giving rise to clinical Lyme borreliosis.
- MeSH
- Borrelia burgdorferi * MeSH
- Borrelia * MeSH
- imunoglobulin G MeSH
- imunoglobulin M MeSH
- lidé MeSH
- lymeská nemoc * epidemiologie MeSH
- protilátky bakteriální MeSH
- průřezové studie MeSH
- senioři MeSH
- séroepidemiologické studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
BACKGROUND: To demonstrate extended protection against meningococcal serogroup B (MenB) disease after MenB-FHbp (bivalent rLP2086) vaccination, this study evaluated immunopersistence through 26 months following MenB-FHbp boosting after 2 or 3 primary doses in adolescents. STUDY DESIGN: This phase 3, open-label study was an extension of 3 phase 2 studies with participants aged 11-18 years randomized to receive primary MenB-FHbp vaccination following 1 of 5 dosing schedules or control. A booster dose was administered 48 months after the primary series. Immunopersistence through 48 months after the last primary dose (persistence stage) and 26 months postbooster (booster stage) was determined by serum bactericidal assays using human complement (hSBAs) against 4 vaccine-heterologous test strains. Safety evaluations included adverse events (AEs) and local and systemic reactions. RESULTS: Overall, 698 and 304 subjects enrolled in the persistence and booster stages, respectively. hSBA titers declined in all groups during 12 months postprimary vaccination, then remained stable through 48 months. One month postbooster, 93.4-100.0% of subjects achieved hSBA titers ≥ lower limit of quantitation against each test strain; percentages at 12 and 26 months postbooster were higher than at similar time points following primary vaccination. Primary and booster MenB-FHbp vaccinations were well tolerated, with ≤ 12.5% of subjects reporting AEs during each stage. The most common local (reported by 84.4-93.8% of subjects) and systemic (68.8-76.6%) reactions to the booster were injection site pain and fatigue and headache, respectively; ≤ 3.7% of subjects reported severe systemic events. CONCLUSION: Protective hSBA titers initially declined but were retained by many subjects for 4 years irrespective of primary MenB-FHbp vaccination schedule. Boosting at 48 months after primary vaccination was safe, well tolerated, and induced immune responses indicative of immunological memory that persisted through 26 months. Booster vaccination during late adolescence may prolong protection against MenB disease.
- MeSH
- imunogenicita vakcíny MeSH
- lidé MeSH
- meningokokové infekce * prevence a kontrola MeSH
- meningokokové vakcíny * škodlivé účinky MeSH
- mladiství MeSH
- Neisseria meningitidis séroskupiny B * MeSH
- protilátky bakteriální MeSH
- séroskupina MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
In Glässer's disease outbreaks, Glaesserella (Haemophilus) parasuis has to overcome the non-specific immune system in the lower respiratory tract, the alveolar macrophages. Here we showed that porcine alveolar macrophages (PAMs) were able to recognize and phagocyte G. parasuis with strain-to-strain variability despite the presence of the capsule in virulent (serovar 1, 5, 12) as well in avirulent strains (serovar 6 and 9). The capsule, outer membrane proteins, virulence-associated autotransporters, cytolethal distending toxins and many other proteins have been identified as virulence factors of this bacterium. Therefore, we immunized pigs with the crude capsular extract (cCE) from the virulent G. parasuis CAPM 6475 strain (serovar 5) and evaluated the role of the anti-cCE/post-vaccinal IgG in the immune response of PAMs to in vitro infection with various G. parasuis strains. We demonstrated the specific binding of the antibodies to the cCE by Western-blotting assay and immunoprecipitation as well as the specific binding to the strain CAPM 6475 in transmission electron microscopy. In the cCE, we identified several virulence-associated proteins that were immunoreactive with IgG isolated from sera of immunized pigs. Opsonization of G. parasuis strains by post-vaccinal IgG led to enhanced phagocytosis of G. parasuis by PAMs at the first two hours of infection. Moreover, opsonization increased the oxidative burst and expression/production of both pro- and anti-inflammatory cytokines. The neutralizing effects of these antibodies on the antioxidant mechanisms of G. parasuis may lead to attenuation of its virulence and pathogenicity in vivo. Together with opsonization of bacteria by these antibodies, the host may eliminate G. parasuis in the infection site more efficiently. Based on these results, the crude capsular extract is a vaccine candidate with immunogenic properties.
- MeSH
- alveolární makrofágy imunologie metabolismus mikrobiologie MeSH
- antigeny bakteriální imunologie MeSH
- bakteriální pouzdra imunologie MeSH
- fagocytóza MeSH
- Haemophilus parasuis imunologie patogenita MeSH
- hemofilové infekce imunologie metabolismus mikrobiologie MeSH
- kinetika MeSH
- kultivované buňky MeSH
- neutralizující protilátky imunologie metabolismus MeSH
- protilátky bakteriální imunologie metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- séroskupina MeSH
- specificita protilátek MeSH
- Sus scrofa MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. METHODS: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7-366/7 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11-18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. RESULTS: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4-1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). CONCLUSIONS: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02853929.
- MeSH
- difterie * prevence a kontrola MeSH
- hemofilové vakcíny * MeSH
- imunita MeSH
- kojenec MeSH
- kombinované vakcíny MeSH
- lidé MeSH
- následné studie MeSH
- pertuse * prevence a kontrola MeSH
- poliovirová vakcína inaktivovaná MeSH
- předškolní dítě MeSH
- protilátky bakteriální MeSH
- sekundární imunizace MeSH
- těhotenství MeSH
- tetanus * prevence a kontrola MeSH
- vakcína proti diftérii, tetanu a pertusi MeSH
- vakcína proti záškrtu, tetanu a černému kašli * MeSH
- vakcinace MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Austrálie MeSH
- Evropa MeSH
- Kanada MeSH
Wild rodents are an important source of the tick-borne pathogens Coxiella burnetii and Francisella tularensis. The aim of our study was to assess the prevalence of antibodies and possible coexistence of these pathogens in wild small mammals from three localities in the Czech Republic. A total of 614 wild small mammals (324 Apodemus flavicollis, 145 Myodes glareolus, 50 Sorex araneus, 48 A. sylvaticus, 40 A. agrarius, six Microtus arvalis and one Talpa europaea) were trapped between 2012 and 2015. Their sera or heart extracts were examined by modified indirect enzyme-linked immunosorbent assay, with the detection of antibodies against C. burnetii and F. tularensis in 12 % and 7 % of animals, respectively; coinfection was identified in 4.4 % of animals. The prevalence of C. burnetii and F. tularensis antibodies statistically differed according to animal species and sex (p < 0.05); the seroprevalence of C. burnetii (p < 0.05) also differed in the sampling period. The highest prevalence of antibodies against C. burnetii and F. tularensis was detected in the case of M. glareolus (24 % and 14 %, respectively).
- MeSH
- Arvicolinae MeSH
- Coxiella burnetii izolace a purifikace MeSH
- Francisella tularensis izolace a purifikace MeSH
- koinfekce epidemiologie mikrobiologie veterinární MeSH
- krtci MeSH
- Murinae MeSH
- nemoci hlodavců epidemiologie mikrobiologie MeSH
- prevalence MeSH
- protilátky bakteriální krev MeSH
- Q-horečka epidemiologie mikrobiologie veterinární MeSH
- rejskovití MeSH
- séroepidemiologické studie MeSH
- tularemie epidemiologie mikrobiologie veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
