Chřipka je velmi závažné onemocnění, které je každoročně pričinou tisíců úmrtí na celém světě. Protože do současné doby neexistuje dostatečně efektivní kauzální léčba chřipky, v prevenci je prioritní především vakcinace. Chripka je velkým problémem především v kolektivních zařízeních. Proto je i v Armádě České republiky kladen důraz na vakcinaci vojenských kolektivů a kontrolu vlastností použitých očkovacích látek. Cílem klinické studie bylo především zhodnocení reaktogenity a imunogenity dvou inaktivovaných štěpených vakcín proti chřipce Fluarix TM a Vaxigrip® mezi zdravými dospělými dobrovolníky ve věku 18 - 60 let s důrazem na vojenské kolektivy. Studie byla plánována jako otevřená klinická studie se 2 skupinanú (každá v jednom centru) po 100 vakcinovaných. Nebyla však provedena randomizace a tak každá skupina dostala jen předem určenou vakcínu. Obě hodnocené inaktivované štěpené vakcíny Vaxigrip® a Fluarix™ jsou vysoce imunogenní jak proti deklarovaným, tak i dalším antigenním variantám chřipky. Studie prokázala priznivý trend pri pripravě chřipkových vakcín projevující se výrazným snížením celkových nežádoucích reakcí oproti předcházejícím letům. Vakcíny i přes drobné rozdíly v imunogenitě a reaktogenitě jsou v globálním pohledu srovnatelné a u zdravých osob ve věku 18-60 let vyvolávají dostatečnou ochranu proti vzniku a rozvoji chřipkového onemocnění. Výsledky naši otevřené klinické studie (bez provedené randomizace) opět potvrdily, že oba výrobci pripravují vakcíny vysokého evropského standardu.

Influenza is a very serious illness annually causing thousands of deaths all over the worid. Since hitherto there is no sufficiently effective causal therapy of influenza, vaccination has top priority in its prevention. Influenza is a grave problem in collective facilities. Therefore in the Army of the Czech Republic emphasis is given to vaccination of military personnel and control of the efficacy of vaccines used. The chief purpose of this clinical investigation was the evaluation of the reactogenicity and immunogenicity of two inactivated split influenza vaccines Fluarix TM and Vaxigrip® among healthy adult volunteers 18 to 60 years of age with emphasis on army groups. The investigation was designed as an open clinical study of two groups (each in one center) per 100 vaccines. There was no randomization, so each group was given only one predetermined vaccine. Both inactivated split vaccines, Fluarix™ and Vaxigrip®, proved highly immunogenic, not only against the declared influenzavirus, but also against its other antigenic variants. The investigation revealed a favorable trend in the preparation of influenza vaccines in that there is a significant decrease of general undesirable reactions among the vaccinated in comparison with preceding years. The vaccines, disregarding minor differences in immunogenicity and reactogenicity, are, in general, comparable and in healthy persons 18 to 60 years of age elicit sufficient protection against infection and development of influenza. Results of our open nonrandomized clinical investigation confirmed again that both producers prepare vaccines of high European standard.

• Klíčová slova
• FLUARIX (SM.KL.BEECH.BIOL.,RIXENSART,BELGIE), VAXIGRIP (PASTEUR MERIÉUX, LYON, FRANCIE),
• MeSH
• chřipka lidská imunologie   prevence a kontrola   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• vakcíny proti chřipce farmakologie   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• hodnotící studie MeSH
• srovnávací studie MeSH

• Klíčová slova
• VAXIGRIP, FLUARIX TM,
• MeSH
• hodnocení léčiv MeSH
• lidé MeSH
• ozbrojené síly MeSH
• vakcinace MeSH
• vakcíny proti chřipce škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• klinické zkoušky MeSH

The immunogenicity and reactogenicity of primary vaccination at 3, 4 and 5 months and boosting at 12-18 months with a new DTPw-HBV vaccine was compared with either licensed DTPw and HBV vaccines given separately or a licensed DTPw-HBV combination (Tritanrix-HepB) in this randomized, partially double-blind primary vaccination and single-blind booster vaccination study in healthy infants (n = 239; Trial DTPw-HBV-001/004). One month after primary vaccination with the new DTPw-HBV vaccine, seroprotection against diphtheria, tetanus, hepatitis B and vaccine response to B. pertussis was seen in 100%, 98.7%, 94.9% and 98.7% of subjects, respectively, compared to 100%, > or =98.5%, 89.2% and 92.2% of subjects in the comparator groups, respectively. One month after the booster dose, a marked response to all vaccine antigens was observed, resulting in seroprotection against diphtheria, tetanus, hepatitis B in all DTPw-HBV recipients and response to B. pertussis in over 98.6%. After primary vaccination, there was evidence that fever > or =38.0 degrees C (rectal route) occurred more frequently after the new vaccine (following 41.6% of doses, compared with 32.2% and 29.3% in the comparator groups, p < 0.05) and that pain and drowsiness occurred more frequently than after licensed DTPw-HBV (45.3% versus 35.1% and 37.1% versus 24.9%, respectively). However after primary and booster doses Grade 3 symptoms occurred at similar frequencies in the three groups suggesting these possible differences are of minimal clinical significance. In conclusion, within the framework of this study the immunogenicity and safety profiles of GSK Biologicals' new DTPw-HBV vaccine when used for primary and booster vaccination were acceptable.

• MeSH
• dvojitá slepá metoda MeSH
• financování organizované MeSH
• hepatitida B - protilátky analýza   MeSH
• kojenec MeSH
• kombinované vakcíny imunologie   škodlivé účinky   MeSH
• lidé MeSH
• protilátky bakteriální MeSH
• sekundární imunizace MeSH
• vakcína proti diftérii, tetanu a pertusi škodlivé účinky   imunologie   MeSH
• vakcína proti hepatitidě B imunologie   škodlivé účinky   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

• MeSH
• bakteriální polysacharidy aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• hepatitida - protilátky krev   MeSH
• hepatitida A aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• inaktivované vakcíny aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• kombinované vakcíny aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• lidé MeSH
• vakcíny proti tyfu a paratyfu aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4-8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742 .

• MeSH
• dospělí MeSH
• Leishmania major * imunologie   MeSH
• leishmanióza kožní * imunologie   parazitologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• parazitární zátěž MeSH
• Phlebotomus parazitologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

• MeSH
• adsorpce MeSH
• bakteriální vakcíny aplikace a dávkování   škodlivé účinky   MeSH
• difterický toxoid MeSH
• difterie prevence a kontrola   MeSH
• dítě MeSH
• erytém etiologie   MeSH
• kojenec MeSH
• lidé MeSH
• pertuse prevence a kontrola   MeSH
• pertusová vakcína MeSH
• tetanový toxoid MeSH
• tetanus prevence a kontrola   MeSH
• tvorba protilátek MeSH
• vakcinace MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH

• Klíčová slova
• VAXIGRIP, FLUARIX,
• MeSH
• chřipka lidská prevence a kontrola   MeSH
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• tvorba protilátek MeSH
• vakcíny proti chřipce MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• klinické zkoušky MeSH

INTRODUCTION: Vaccination with formulations containing pneumococcal protein antigens such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) may extend serotype-related protection of pneumococcal conjugate vaccines (PCVs) against Streptococcus pneumoniae. METHODS: This phase II, multi-center, observer-blind trial conducted in Europe (NCT01204658) assessed 2 investigational vaccines containing 10 serotype-specific polysaccharide conjugates of PHiD-CV and either 10 or 30µg of dPly and PhtD each. Infants randomized 1:1:1:1 received 4 doses of PHiD-CV/dPly/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, or 13-valent PCV (PCV13), co-administered with DTPa-HBV-IPV/Hib, at ages ∼2, 3, 4 and 12-15months. Occurrences of fever >40.0°C following primary vaccination with PHiD-CV/dPly/PhtD vaccines compared to PHiD-CV (non-inferiority objective), dose superiority, safety and immunogenicity were assessed. RESULTS: 575 children received primary vaccination, and 564 booster vaccination. The non-inferiority objective was met; no fever >40.0°C causally related to vaccination was reported during primary vaccination. Incidence of adverse events appeared similar between the 3 PHiD-CV groups. Serious adverse events were reported in 13, 9, 21 (1 related to vaccination), and 17 children in the PHiD-CV/dPly/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, and PCV13 groups, respectively. PHiD-CV/dPly/PhtD-30 was superior to PHiD-CV/dPly/PhtD-10 in terms of post-dose 3 anti-Ply and Anti-PhtD antibody levels. Anti-Ply and anti-PhtD antibody levels were higher in both PHiD-CV/dPly/PhtD groups than in controls and increased from post-primary to post-booster timepoint. Post-primary and booster vaccination, for each PHiD-CV serotype, ≥98.5% of participants in PHiD-CV/dPly/PhtD groups had antibody concentrations ≥ 0.2μg/mL, except for 6B (≥72.3%) and 23F (≥82.7%) post-primary vaccination. Similar results were observed in the PHiD-CV group. Immune responses to protein D and DTPa-HBV-IPV/Hib were within similar ranges for the 3 PHiD-CV groups. CONCLUSION: Both PHiD-CV/dPly/PhtD formulations co-administered with DTPa-HBV-IPV/Hib in infants were well-tolerated and immunogenic for dPly and PhtD antigens, while immune responses to serotype-specific, protein D and co-administered antigens did not appear altered in comparison to PHiD-CV group.

• MeSH
• bakteriální proteiny imunologie   MeSH
• horečka etiologie   MeSH
• imunogenicita vakcíny * MeSH
• kojenec MeSH
• kombinované vakcíny imunologie   MeSH
• lidé MeSH
• pneumokokové infekce prevence a kontrola   MeSH
• pneumokokové vakcíny aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• protilátky bakteriální krev   MeSH
• sekundární imunizace MeSH
• séroskupina MeSH
• Streptococcus pneumoniae chemie   imunologie   MeSH
• streptolysiny imunologie   MeSH
• vakcinace MeSH
• vakcíny konjugované imunologie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

• MeSH
• dítě MeSH
• kojenec MeSH
• kombinované vakcíny imunologie   terapeutické užití   MeSH
• lidé MeSH
• spalničková vakcína imunologie   terapeutické užití   MeSH
• tvorba protilátek MeSH
• vakcína proti příušnicím imunologie   terapeutické užití   MeSH
• vakcína proti zarděnkám imunologie   terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• Geografické názvy
• Běloruská republika MeSH

BACKGROUND: A multicomponent meningococcal serogroups ABCWY vaccine (MenABCWY) could provide broad protection against disease-causing meningococcal strains and simplify the immunisation schedule. The aim of this trial was to confirm the effect of the licensed meningococcal serogroup B (MenB) vaccine, 4CMenB, against diverse MenB strains, and to assess the breadth of immune response against a panel of 110 MenB strains for MenABCWY containing the antigenic components of 4CMenB and licensed serogroups ACWY vaccine, MenACWY-CRM, the non-inferiority of the immune response with MenABCWY versus 4CMenB and MenACWY-CRM, safety, and MenABCWY lot-to-lot consistency. METHODS: We conducted a phase 3 randomised, controlled, observer-blinded trial of healthy adolescents and young adults (age 10-25 years) across 114 centres in Australia, Canada, Czechia, Estonia, Finland, Türkiye, and the USA. Exclusion criteria included previous vaccination with a MenB vaccine or (within the last 4 years) MenACWY vaccine. Participants were randomly allocated (5:5:3:3:3:1 ratio) via a central randomisation system using a minimisation procedure to receive 4CMenB at months 0, 2, and 6 (referred to as 4CMenB 0-2-6 hereafter); or 4CMenB at months 0 and 6 (referred to as 4CMenB 0-6 hereafter); or MenABCWY (three groups, each receiving one production lot of the MenACWY-CRM component) at months 0 and 6; or MenACWY-CRM at month 0. Demonstration in the per-protocol set of the consistency of three MenACWY-CRM component lots of the MenABCWY vaccine was a primary objective (demonstrated with two-sided 95% CIs for the ratio of human serum bactericidal antibody [hSBA] geometric mean titres against each serogroup within predefined criteria [0·5-2·0]). The primary endpoints (breadth of immune response) for the MenB component of MenABCWY and 4CMenB were measured using the endogenous complement hSBA (enc-hSBA) assay against a panel of 110 diverse MenB invasive disease strains. For each serum sample, 35 strains from the 110 MenB strain panel were randomly selected for testing. The 4CMenB breadth of immune response data have been published separately. For MenABCWY, breadth of immune response was assessed in two analyses: a test-based analysis of the percentage of samples (tests) without bactericidal serum activity against MenB strains 1 month after two MenABCWY doses versus the percentage after one MenACWY-CRM dose in the per-protocol set, and a responder-based analysis of the percentage of participants (responders) whose sera killed 70% or more strains at 1 month after two MenABCWY doses in the full analysis set. A lower limit of two-sided 95% CI above 65% would demonstrate breadth of immune response. Other primary outcomes included non-inferiority (5% margin) of two MenABCWY doses versus two 4CMenB doses by enc-hSBA assay in the per-protocol set, non-inferiority (10% margin) of two MenABCWY doses versus one MenACWY-CRM dose in MenACWY vaccine-naive participants by traditional hSBA assay in the per-protocol set, and safety in all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT04502693, and is complete. FINDINGS: Between Aug 14, 2020, and Sept 3, 2021, 3651 participants were enrolled and randomly allocated (900 in the 4CMenB 0-2-6 group and 908 in the 4CMenB 0-6 group, 1666 in the three MenABCWY groups combined, and 177 in the MenACWY-CRM group). All primary objectives for MenABCWY were met. Consistency of immune responses against the three production lots of the MenACWY component of MenABCWY was demonstrated since two-sided 95% CIs for the ratios of hSBA geometric mean titres against serogroups A, C, W, and Y for each pair of lots were within the predefined equivalence criteria. The lot data were pooled for the remainder of MenABCWY endpoints. By enc-hSBA assay, breadth of immune response against the MenB strain panel was 77·9% (95% CI 76·6 to 79·2) in the test-based analysis and 84·1% (81·4 to 86·5; 687 of 817 participants) in the responder-based analysis. Non-inferiority of MenABCWY to 4CMenB was demonstrated by enc-hSBA assay: the difference in percentage of samples with bactericidal serum activity between the MenABCWY group (82·5% [95% CI 82·1 to 83·0]; 21 222 of 25 715) and 4CMenB 0-2 group (83·1% [82·7 to 83·6]; 22 921 of 27 569) was -0·61% (-1·25 to 0·03). Non-inferiority of two-dose MenABCWY to one-dose MenACWY-CRM was demonstrated by traditional hSBA assay, with differences between the MenABCWY group and MenACWY group in percentages of participants with a four-fold rise in hSBA titres of 11·3% (5·9 to 19·0) for serogroup A, 47·2% (38·1 to 56·3) for serogroup C, 35·3% (26·9 to 44·5) for serogroup W, and 27·0% (19·4 to 35·8) for serogroup Y. MenABCWY reactogenicity was mostly of mild or moderate severity and transient, with similar frequencies of adverse events in the MenABCWY and 4CMenB groups and no safety concerns were identified. INTERPRETATION: This study demonstrates breadth of immune response against a panel of 110 MenB strains for the MenB component of the investigational MenABCWY vaccine, when administered as a 0-6 months schedule to the target population of adolescents and young adults, with predefined criteria for success met for both breadth of immune response endpoints and for non-inferiority versus 4CMenB. This investigational vaccine could provide broad meningococcal serogroup coverage in a simplified immunisation schedule, thus aiding the public health attempt in preventing invasive meningococcal disease due to five Neisseria meningitidis serogroups in adolescents and young adults. FUNDING: GSK.

• MeSH
• dítě MeSH
• dospělí MeSH
• imunogenicita vakcíny * MeSH
• jednoduchá slepá metoda 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 séroskupiny B imunologie   MeSH
• Neisseria meningitidis imunologie   MeSH
• protilátky bakteriální krev   MeSH
• zdraví dobrovolníci pro lékařské studie 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
• hodnocení ekvivalence MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH