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

Invazivní meningokoková onemocnění patří mezi nejzávažnější infekční onemocnění s vysokou smrtností a četným zastoupením těžkých celoživotních následků u přeživších pacientů. Zákeřností tohoto onemocnění je fakt, že ke vzniku závažného klinického stavu mnohdy dochází často z plného zdraví během několika hodin, přičemž počáteční příznaky jsou většinou velmi nespecifické a nenasvědčují pro rozvoj život ohrožujícího stavu. I pro zkušeného lékaře může být úvodní diagnostika obtížná, o čemž pojednává níže předkládaná kazuistika a zdůrazňuje význam prevence, resp. očkování.

Invasive meningococcal disease is among the most serious infectious diseases with high mortality and a high percentage of severe lifelong consequences for patients who survive. The insidious nature of this disease is that a servus clinical condition often develops within hours from apparent good health, and initial symptoms are usually nonspecific and do not indicate the development of a life-threatening condition. Even experienced doctors may not recognize this disease in time; therefore prevention, vaccination respectively, is crucial. The presented article is based on case report.

• MeSH
• dítě MeSH
• lidé MeSH
• meningokokové infekce * diagnóza   farmakoterapie   prevence a kontrola   MeSH
• meningokokové vakcíny MeSH
• rizikové faktory MeSH
• séroskupina MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

V programu surveillance byl v roce 2023 zjištěn v České republice pokles počtu invazivních meningokokových onemocnění oproti předchozímu roku: celkem 16 (nemocnost 0,15/100 000 obyv.) proti 25 v roce 2022 (nemocnost 0,24/100000 obyv.). Z 16 onemocnění v roce 2023 jedno skončilo úmrtím – celková smrtnost 6,25 %. Toto úmrtí způsobila séroskupina Y ve věkové skupině nad 65 let věku. Podobně jako v předchozím roce převažovala i v roce 2023 onemocnění způsobená Neisseria meningitidis B (8 ze 16), čtyři onemocnění byla způsobená séroskupinou C a po jednom onemocnění způsobily séroskupiny A aY. U dvou případů nebyla séroskupina určena: N. meningitidis ND. V roce 2023 došlo ve srovnání s předchozím rokem k výraznému poklesu nemocnosti v nejmladší věkové skupině 0–11měsíčních (na 1,96/100 000 z 5,37/100000 obyv.). Nemocnost v nejmladší věkové skupině klesla u onemocnění způsobeného séroskupinou B (na 0,98/100 000 z 3,58/100000 obyv.) i u séroskupin preventabilních konjugovanou tetravakcínou A, C, W, Y (na 0,98/100 000 z 1,79/100000 obyv.). Ve věkové skupině 1–4letých nemocnost v roce 2023 mírně klesla oproti předchozímu roku (na 0,43/100 000 z 0,67/100000 obyv.) a byla způsobena pouze séroskupinou B. Ve věkové skupině 15–19 letých v roce 2023 nemocnost poklesla oproti předchozímu roku (na 0,18/100 000 z 0,79/100 000 obyv.) a byla rovněž způsobena pouze séroskupinou B. Z 16 invazivních meningokokových onemocnění v roce 2023 bylo 9 prokázáno pouze kultivačně, 2 kultivačně a metodou PCR, 5 pouze metodou PCR. V roce 2023 byla v Národní referenční laboratoři provedena multilokusová sekvenční typizace (MLST) u všech 9 kmenů z invazivního meningokokového onemocnění, které byly do NRL pro meningokokové nákazy poslány. MLST prokázala heterogenitu izolátů způsobujících IMO: celkem bylo zjištěno 5 hypervirulentních klonálních komplexů, z nich nejčastější byl cc103 (3 izoláty), následovaný cc11, cc213, cc23 a cc41/44 (vždy po jednom izolátu). MLST analýze byl podroben také jeden izolát od kontaktu s IMO s výsledkem cc103.

In the surveillance programme, a decrease in the number of invasive meningococcal diseases (IMD) was detected in the Czech Republic in 2023 compared to the previous year: a total of 16 (incidence 0.15/100000) compared to 25 in 2022 (incidence 0.24/100000). Of the 16 cases in 2023, one resulted in death – an overall case fatality rate was 6.25%. This death was caused by serogroup Y in the age group over 65 years. As in the previous year, Neisseria meningitidis B accounted for the majority of cases in 2023 (8 out of 16), four cases were caused by serogroup C and one case each by serogroups A and Y. In two cases, the serogroup was not determined: N. meningitidis ND. In 2023, there was a significant decrease in the morbidity in the youngest age group 0–11 months (to 1.96/100,000 from 5.37/100,000) compared to the previous year. Morbidity in the youngest age group decreased for serogroup B (to 0.98/100,000 from 3.58/100,000) and for serogroups preventable with conjugate tetravaccine A, C, W, Y (to 0.98/100,000 from 1.79/100,000). In the age group 1–4 years old, the morbidity in 2023 decreased slightly compared to the previous year (to 0.43/100,000 from 0.67/100,000) and was caused only by serogroup B. In the age group 15–19 years old, the morbidity in 2023 decreased compared to the previous year (to 0.18/100 000 from 0.79/100000) and was also due to serogroup B only. Of the 16 invasive meningococcal disease cases in 2023, 9 were proven by culture only, 2 by culture and PCR, and 5 by PCR only. In 2023, multilocus sequence typing (MLST) was performed for all the 9 strains from the invasive meningococcal disease cases sent to the National Reference Laboratory for Meningococcal Infections. MLST demonstrated heterogeneity of the isolates causing IMD: a total of 5 hypervirulent clonal complexes were identified, the most common being cc103 (3 isolates), followed by cc11, cc213, cc23 and cc41/44 (one isolate each). One isolate from the IMD contact was also subjected to MLST analysis with the result of cc103.

• MeSH
• lidé MeSH
• meningokokové infekce * epidemiologie   mortalita   prevence a kontrola   MeSH
• meningokokové vakcíny MeSH
• Neisseria meningitidis izolace a purifikace   klasifikace   MeSH
• polymerázová řetězová reakce MeSH
• séroskupina MeSH
• surveillance populace MeSH
• věkové rozložení MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• grafy a diagramy MeSH
• Geografické názvy
• Česká republika MeSH

Invasive meningococcal disease (IMD) is an acute life-threatening infection caused by the gram-negative bacterium, Neisseria meningitidis. Globally, there are approximately half a million cases of IMD each year, with incidence varying across geographical regions. Vaccination has proven to be successful against IMD, as part of controlling outbreaks, and when incorporated into national immunization programs. The South-Eastern Europe Meningococcal Advocacy Group (including representatives from Croatia, the Czech Republic, Greece, Hungary, Poland, Romania, Serbia, Slovenia and Ukraine) was formed in order to discuss the potential challenges of IMD faced in the region. The incidence of IMD across Europe has been relatively low over the past decade; of the countries that came together for the South-Eastern Meningococcal Advocacy Group, the notification rates were lower than the European average for some country. The age distribution of IMD cases was highest in infants and children, and most countries also had a further peak in adolescents and young adults. Across the nine included countries between 2010 and 2020, the largest contributors to IMD were serogroups B and C; however, each individual country had distinct patterns for serogroup distribution. Along with the variations in epidemiology of IMD between the included countries, vaccination policies also differ.

• MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• meningokokové infekce * epidemiologie   prevence a kontrola   mikrobiologie   MeSH
• meningokokové vakcíny * MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Neisseria meningitidis * MeSH
• séroskupina MeSH
• vakcinace MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Evropa MeSH

• MeSH
• dítě MeSH
• lidé MeSH
• meningokokové infekce * diagnóza   komplikace   prevence a kontrola   MeSH
• meningokokové vakcíny farmakologie   terapeutické užití   MeSH
• Neisseria meningitidis imunologie   patogenita   ultrastruktura   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• 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

• MeSH
• dítě MeSH
• kombinované vakcíny MeSH
• lidé MeSH
• meningokokové infekce * epidemiologie   prevence a kontrola   MeSH
• meningokokové vakcíny terapeutické užití   MeSH
• očkovací schéma MeSH
• syntetické vakcíny MeSH
• vakcíny konjugované MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• směrnice pro lékařskou praxi MeSH

• MeSH
• aktivní imunita MeSH
• infekce dýchací soustavy prevence a kontrola   MeSH
• lidé MeSH
• meningokokové vakcíny * terapeutické užití   MeSH
• Neisseria meningitidis * imunologie   izolace a purifikace   patogenita   MeSH
• odolnost vůči nemocem imunologie   MeSH
• respirační sliznice * fyziologie   MeSH
• Check Tag
• lidé MeSH

• MeSH
• dítě MeSH
• kombinované vakcíny MeSH
• lidé MeSH
• meningokokové vakcíny MeSH
• očkovací schéma MeSH
• pneumokokové vakcíny MeSH
• poliovirové vakcíny MeSH
• povinné očkování MeSH
• statistika jako téma MeSH
• vakcína proti spalničkám, příušnicím a zarděnkám MeSH
• vakcína proti záškrtu, tetanu a černému kašli MeSH
• vakcinace * statistika a číselné údaje   zákonodárství a právo   MeSH
• vakcíny proti papilomavirům MeSH
• vakcíny ekonomika   klasifikace   zásobování a distribuce   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH

Invasive meningococcal disease belongs among the most dangerous infectious diseases in the world. Several polysaccharide conjugate vaccines against serogroups A, C, W and Y are available and two recombinant peptide vaccines against serogroup B (MenB vaccines) have been developed: MenB-4C (Bexsero) and MenB-fHbp (Trumenba). The aim of this study was to define the clonal composition of the Neisseria meningitidis population in the Czech Republic, to determine changes in this population over time and to estimate the theoretical coverage of isolates by MenB vaccines. This study presents the analysis of whole genome sequencing data of 369 Czech N. meningitidis isolates from invasive meningococcal disease covering 28 years. Serogroup B isolates (MenB) showed high heterogeneity and the most common clonal complexes were cc18, cc32, cc35, cc41/44, and cc269. Isolates of clonal complex cc11 were predominately serogroup C (MenC). The highest number of serogroup W isolates (MenW) belonged to clonal complex cc865, which we described as exclusive to the Czech Republic. Our study supports the theory that this cc865 subpopulation originated in the Czech Republic from MenB isolates by a capsule switching mechanism. A dominant clonal complex of serogroup Y isolates (MenY) was cc23, which formed two genetically quite distant subpopulations and which showed constant representation throughout the observed period. The theoretical coverage of isolates by two MenB vaccines was determined using the Meningococcal Deduced Vaccine Antigen Reactivity Index (MenDeVAR). Estimated Bexsero vaccine coverage was 70.6% (for MenB) and 62.2% (for MenC, W, Y). For Trumenba vaccine, estimated coverage was 74.6% (for MenB) and 65.7% (for MenC, W, Y). Our results demonstrated sufficient coverage of Czech heterogeneous population of N. meningitidis with MenB vaccines and, together with surveillance data on invasive meningococcal disease in the Czech Republic, were the basis for updating recommendations for vaccination against invasive meningococcal disease.

• MeSH
• antigeny bakteriální MeSH
• lidé MeSH
• meningokokové infekce * epidemiologie   MeSH
• meningokokové vakcíny * MeSH
• Neisseria meningitidis séroskupiny B * genetika   MeSH
• Neisseria meningitidis * MeSH
• sekvenování celého genomu MeSH
• séroskupina MeSH
• syntetické vakcíny genetika   MeSH
• vakcinace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH