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

• MeSH
• antibiotická profylaxe MeSH
• hemofilové vakcíny terapeutické užití   MeSH
• lidé MeSH
• meningokokové vakcíny terapeutické užití   MeSH
• následná péče organizace a řízení   MeSH
• nemoci sleziny imunologie   MeSH
• očkovací schéma MeSH
• pneumokokové vakcíny terapeutické užití   MeSH
• protilátky bakteriální analýza   imunologie   MeSH
• splenektomie * MeSH
• streptokokové vakcíny terapeutické užití   MeSH
• Check Tag
• lidé MeSH

Background: Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost preexisting neutralizing antibody titers, providing passive protection to newborns. Methods: Two observer-blinded, controlled studies (RSV F-020 [clinical trials registration NCT02360475] and RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, nonpregnant 18-45-year-old women. Both studies used a licensed adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis (Tdap) vaccine as a control. RSV F-020 evaluated immunogenicity and safety: participants were randomized (1:1:1:1) to receive 1 dose of RSV-prefusion F protein (PreF) vaccine containing 30 µg or 60 µg of nonadjuvanted RSV-PreF, 60 µg of aluminum-adjuvanted RSV-PreF, or Tdap. RSV F-024 evaluated safety: participants were randomized 1:1 to receive 1 dose of 60 µg of nonadjuvanted RSV-PreF or Tdap. Results: Both studies showed similar reactogenicity profiles for RSV-PreF and Tdap. No serious adverse events were considered vaccine related. In RSV F-020, geometric mean ratios of RSV-A neutralizing antibody levels at day 30 versus prevaccination were 3.1-3.9 in RSV-PreF recipients and 0.9 in controls. Palivizumab-competing antibody concentrations increased >14-fold in RSV-PreF recipients on day 30. RSV antibody titers waned after day 30 but remained well above baseline through day 90. Conclusions: All formulations of RSV-PreF boosted preexisting immune responses in 18-45-year old women with comparable immunogenicity. The RSV-PreF safety profile was similar to that of Tdap vaccine.

• MeSH
• adjuvancia imunologická farmakologie   MeSH
• dospělí MeSH
• imunogenicita vakcíny imunologie   MeSH
• infekce respiračními syncytiálními viry imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský respirační syncytiální virus imunologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neutralizující protilátky imunologie   MeSH
• pertuse imunologie   MeSH
• protilátky bakteriální imunologie   MeSH
• protilátky virové imunologie   MeSH
• vakcína proti diftérii, tetanu a pertusi imunologie   MeSH
• vakcína proti záškrtu, tetanu a černému kašli imunologie   MeSH
• vakcinace metody   MeSH
• vakcíny proti respiračnímu syncyciálnímu viru škodlivé účinky   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Individuals with functional or anatomic asplenia are at high risk for meningococcal disease. We evaluated the immunogenicity and safety of 1 and 2 doses of the quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid-conjugate vaccine (MenACWY-TT) in this high-risk population. METHODS: This phase III, open-label, controlled, non-randomized study (NCT01641042) enrolled 1-17-year-olds with impaired splenic activity (high-risk group) and age-matched healthy controls (control group). We measured immune responses to MenACWY-TT by serum bactericidal activity assays using rabbit (rSBA) and human (hSBA) complement and in terms of antibodies against polysaccharides of the 4 vaccine serogroups. We evaluated vaccine response rates (VRRs) as 4-fold increases from pre-vaccination levels or titers ≥1:32 (rSBA)/≥1:8 (hSBA). We recorded solicited and unsolicited adverse events (AEs) during 4 and 31 days post-vaccination, and serious AEs (SAEs) and new onset of chronic illnesses (NOCIs) throughout the study. RESULTS: The according-to-protocol cohort for immunogenicity included 40 participants per group. In both groups, the first MenACWY-TT dose induced rSBA VRRs of 92.5-100% and hSBA VRRs of 55.6-77.1% across vaccine serogroups. Following the second MenACWY-TT dose, all participants had high responses, with rSBA and hSBA VRRs of 73.0-100% across vaccine serogroups. rSBA and hSBA geometric mean titers for each serogroup increased in both groups (with different magnitudes, but ≥13.1-fold) compared with baseline levels. Polysaccharide antibody concentrations ≥2.0 μg/ml were detected in ≥84.4% of participants and were similar between groups. Incidences of solicited and unsolicited AEs were comparable between groups. We recorded SAEs in 4/43 participants in the high-risk group and 1/43 participants in the control group (none vaccine-related). No NOCIs were reported. CONCLUSION: In this descriptive study, MenACWY-TT induced similar functional and humoral immune responses and had a clinically acceptable safety profile in children and adolescents with impaired splenic activity and in healthy controls.

• MeSH
• baktericidní aktivita krve imunologie   MeSH
• dítě MeSH
• incidence MeSH
• kohortové studie MeSH
• komplement imunologie   MeSH
• králíci MeSH
• lidé MeSH
• meningokokové infekce imunologie   MeSH
• meningokokové vakcíny škodlivé účinky   imunologie   MeSH
• mladiství MeSH
• Neisseria meningitidis imunologie   MeSH
• předškolní dítě MeSH
• protilátky bakteriální imunologie   MeSH
• séroskupina MeSH
• tetanový toxoid imunologie   MeSH
• tvorba protilátek imunologie   MeSH
• vakcinace metody   MeSH
• vakcíny konjugované škodlivé účinky   imunologie   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• králíci MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Coxiella burnetii (C. burnetii) is the etiological agent of a Q fever-the re-emerging disease with considerable economic impact. Due to many similar symptoms with commonly occurring infections, its clinical diagnosis is very difficult. Thus, a strong effort should be taken to raise the awareness and develop a robust strategy for an accurate diagnosis. The identification of specific C. burnetii biomarkers could be valuable for a sensitive and selective diagnosis of the disease. Herein, we described a workflow to identify immunoreactive proteins of C. burnetii with a high confidence. It is based on immunocapturing of bacterial antigens by biofunctionalized magnetic microspheres, followed by tandem mass spectrometry (MS/MS) identification. We detected dozens of previously reported antigens and proposed 15 novel biomarkers, which specificity was confirmed by in silico epitope analysis. Among them, the cardiolipin synthetase participating in the synthesis of cardiolipin was recognized. This biomarker could play a critical role in the early management of acute Q fever and prevention of Q fever endocarditis.

• MeSH
• antigeny bakteriální analýza   krev   imunologie   MeSH
• bakteriální proteiny analýza   krev   imunologie   MeSH
• chromatografie kapalinová MeSH
• Coxiella burnetii imunologie   MeSH
• imobilizační protilátky krev   chemie   imunologie   MeSH
• lidé MeSH
• proteomika MeSH
• protilátky bakteriální krev   chemie   imunologie   MeSH
• Q-horečka krev   diagnóza   imunologie   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Although both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity. METHODS: Two phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12-15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11-12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1month post-booster. RESULTS: A total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study. CONCLUSIONS: Overall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27).

• MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• pneumokokové infekce imunologie   prevence a kontrola   MeSH
• pneumokokové vakcíny imunologie   terapeutické užití   MeSH
• protilátky bakteriální imunologie   MeSH
• sekundární imunizace metody   MeSH
• séroskupina MeSH
• vakcíny konjugované imunologie   terapeutické užití   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

Various meningococcal conjugate vaccines exist against serogroups A, C, W and Y. A new protein-based vaccine targeting serogroup B (MenB) is also now available. The potential of such vaccines to drive serogroup replacement is considered a possible public health concern when implementing nationwide routine immunization programmes. The aim of this work was to investigate if and how serogroup replacement may occur following widespread vaccination with a MenB vaccine that may protect against carriage. To that end, we built a dynamic transmission model with age and serogroup stratification, focusing on European settings where most invasive meningococcal disease (IMD) cases are caused by serogroups B and C. For illustration purposes, the model was employed in 2 such settings: UK (England and Wales) and Czech Republic. Preliminary model-based projections suggest that, under strong serogroup competition for colonization, vaccine-induced serogroup replacement may occur even with a relatively low vaccine efficacy against serogroup B carriage (e.g., 20%), with potential subsequent increase in serogroup C IMD. The magnitude and speed of the model-projected serogroup C IMD increase depend on the MenB vaccination strategy, vaccine efficacy against carriage and the extent of any potential cross-protection against other serogroups. These analyses are neither exhaustive nor definitive, and focused on simulating potential population-level trends in IMD post-vaccination, under certain assumptions. Due to present inherent limitations and uncertainties, this study has limited quantitative value and is best regarded as an explorative qualitative modeling approach, to complement and challenge the current status quo, and suggest areas where collecting additional data may be essential.

• MeSH
• dítě MeSH
• hromadná vakcinace MeSH
• kojenec MeSH
• lidé MeSH
• meningokoková meningitida mikrobiologie   prevence a kontrola   MeSH
• meningokokové vakcíny imunologie   MeSH
• mladiství MeSH
• Neisseria meningitidis séroskupiny B imunologie   MeSH
• Neisseria meningitidis séroskupiny C imunologie   MeSH
• předškolní dítě MeSH
• protilátky bakteriální imunologie   MeSH
• teoretické modely MeSH
• vakcinace MeSH
• zkřížená ochrana imunologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Spojené království MeSH

• Klíčová slova
• adaptace patogenu, multiplexová analýza,
• MeSH
• acelulární vakcíny aplikace a dávkování   imunologie   MeSH
• bakteriologické techniky MeSH
• Bordetella parapertussis izolace a purifikace   MeSH
• Bordetella pertussis * imunologie   izolace a purifikace   patogenita   MeSH
• dítě MeSH
• dospělí MeSH
• ELISA MeSH
• faktory virulence rodu Bordetella MeSH
• imunita získaná od matky imunologie   MeSH
• incidence MeSH
• infekce bakteriemi rodu Bordetella diagnóza   imunologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• novorozenec MeSH
• očkovací schéma MeSH
• odběr biologického vzorku MeSH
• pertuse * diagnóza   epidemiologie   imunologie   prevence a kontrola   MeSH
• pertusová vakcína aplikace a dávkování   imunologie   MeSH
• pertusový toxin imunologie   MeSH
• protilátky bakteriální imunologie   krev   MeSH
• sekundární imunizace MeSH
• sérologické testy metody   MeSH
• těhotenství imunologie   MeSH
• vakcína proti záškrtu, tetanu a černému kašli aplikace a dávkování   imunologie   MeSH
• vakcinace MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství imunologie   MeSH
• ženské pohlaví MeSH

Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag) OspC (rOspC) could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC-specific antibodies vary substantially depending upon whether rOspC possesses an N' or C' terminal His-tag. This is the case in mice immunized: (a) with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b) with free rOspC and Montanide PET GEL A; (c) with free rOspC and alum; or (d) with adjuvant-free rOspC. Stronger responses are noted with all N'-terminal His-tag rOspC formulations. OspC-specific Th1-type antibodies predominate post-immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N' and C' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N' to C' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants.

• MeSH
• adjuvancia imunologická * MeSH
• antigeny bakteriální aplikace a dávkování   chemie   imunologie   MeSH
• Borrelia burgdorferi imunologie   MeSH
• ELISA MeSH
• imunizace MeSH
• lymeská nemoc imunologie   MeSH
• modely u zvířat MeSH
• myši MeSH
• proteiny vnější bakteriální membrány aplikace a dávkování   chemie   imunologie   MeSH
• proteolipidy MeSH
• protilátky bakteriální imunologie   MeSH
• rekombinantní fúzní proteiny aplikace a dávkování   chemie   imunologie   izolace a purifikace   MeSH
• sekundární struktura proteinů MeSH
• specificita protilátek imunologie   MeSH
• stabilita proteinů MeSH
• tvorba protilátek imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: A serogroup B meningococcal vaccine (4CMenB) is licensed for infant use in countries including Canada, Australia and those of the European Union. Data on serum bactericidal antibody (hSBA) waning and the ideal timing of a "toddler" booster dose are essential to optimize vaccine utilization. METHODS: An open-labeled, multicenter phase-2b follow-on European study conducted from 2009 to 2012. Participants previously receiving 4CMenB with routine vaccines at 2, 4 and 6 or 2, 3 and 4 months (246Con and 234Con) or at 2, 4 and 6 months intercalated with routine vaccines (246Int) received a booster dose at 12, 18 or 24 months. 4CMenB-naïve "Control" participants aged 12, 18 or 24 months received 2 doses of 4CMenB 2 months apart. RESULTS: One thousand five hundred eighty-eight participants were recruited. At 12 months, before any booster doses, the proportions with hSBA titers ≥1:5 for strain 44/76-SL (testing vaccine component fHBP) were 73% (120/165) for the "246Con" group, 85% (125/147) for "246Int," 57% (51/90) for "234Con" and 13% (26/199) for Controls. For strain 5/99 (NadA) proportions were ≥96% (all 4CMenB-recipients) and 1% (Controls). For strain NZ98/254 (PorA), these were 18-35% (4CMenB-recipients) and 1% (Controls). By 24 months, 4CMenB-recipient proportions were 13-22% (44/76-SL), 82-94% (5/99) and 7-13% (NZ98/254) and in controls ≤4%. After a 12-month booster-dose, ≥95% of previously immunized participants had titers ≥1:5 (all strains). CONCLUSIONS: A 4CMenB booster-dose can overcome waning hSBA titers after early-infant immunization. Administration at 12 months could help to maintain immunity during an age of high risk, and the persistence of this response requires further study.

• MeSH
• hodnocení výsledků zdravotní péče MeSH
• kojenec MeSH
• lidé MeSH
• meningokoková meningitida prevence a kontrola   MeSH
• meningokokové vakcíny aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• Neisseria meningitidis séroskupiny B imunologie   MeSH
• očkovací schéma MeSH
• předškolní dítě MeSH
• protilátky bakteriální krev   imunologie   MeSH
• sekundární imunizace * MeSH
• vakcinace MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH