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
- Klíčová slova
- skórovací systém CURB 65, skorovací systém PSI,
- MeSH
- antibakteriální látky farmakologie klasifikace terapeutické užití MeSH
- C-reaktivní protein analýza MeSH
- komorbidita * MeSH
- lidé MeSH
- pneumokokové vakcíny * MeSH
- pneumonie pneumokoková * diagnostické zobrazování diagnóza farmakoterapie prevence a kontrola MeSH
- senioři MeSH
- Streptococcus pneumoniae patogenita účinky léků MeSH
- vakcíny konjugované terapeutické užití MeSH
- výzkumný projekt MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- Vaxneuvance,
- MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- pneumokokové infekce epidemiologie prevence a kontrola MeSH
- pneumokokové vakcíny * aplikace a dávkování terapeutické užití MeSH
- Streptococcus pneumoniae patogenita MeSH
- vakcinace metody MeSH
- vakcíny konjugované aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé 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
- dítě MeSH
- lidé MeSH
- meningokoková meningitida * epidemiologie mortalita prevence a kontrola MeSH
- meningokokové vakcíny * aplikace a dávkování terapeutické užití MeSH
- Neisseria meningitidis patogenita MeSH
- vakcinace statistika a číselné údaje MeSH
- vakcíny konjugované aplikace a dávkování terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
V období 2006-2022 bylo v České republice hlášeno v programu surveillance 958 případů invazivního meningokokového onemocnění (IMO), z nichž bylo u 21 (2,19 %) hlášeno v anamnéze očkování některou z vakcín proti meningokokovým onemocněním. Analýza dat ukazuje, že tyto vakcíny velmi dobře chrání proti IMO. Nejčastější bylo zjištění, že u pacientů s IMO, kteří měli v anamnéze očkování proti tomuto onemocnění, se jednalo o absenci očkování proti dané séroskupině a/nebo nedošlo k přeočkování. Výsledky této analýzy upozorňují na vhodnost aplikace obou vakcín, které jsou v České republice dostupné: rekombinantní vakcína obsahující antigeny meningokoka séroskupiny B (vakcína MenB) a konjugovaná tetravalentní vakcína obsahující antigeny čtyř séroskupin meningokoka A, C, W, Y (konjugovaná vakcína A, C, W, Y). Výsledky rovněž upozorňují na vhodnost přeočkování vakcínami proti meningokokovým onemocněním a na nezbytnost co nejvčasnějšího očkování vakcínou MenB u malých dětí.
In 2006–2022, 958 cases of invasive meningococcal disease (IMD) were reported to the surveillance programme in the Czech Republic, of which 21 (2.19%) had a history of vaccination with one of the meningococcal vaccines. Data analysis shows that these vaccines provide a very good protection against IMD. It was found that vaccinated patients with IMD either were not vaccinated against the causative serogroup and/or did not receive a booster dose. The results of this analysis show the benefit of both vaccines available in the Czech Republic: recombinant vaccine containing meningococcal serogroup B antigens (MenB vaccine) and tetravalent conjugate vaccine containing antigens of four meningococcal serogroups A, C, W, Y (A, C, W, Y conjugate vaccine). The results also show the benefit of meningococcal vaccine booster doses and the need for giving MenB vaccine to young children as early as possible.
- MeSH
- lidé MeSH
- meningokokové infekce * epidemiologie prevence a kontrola MeSH
- meningokokové vakcíny terapeutické užití MeSH
- Neisseria meningitidis MeSH
- surveillance populace MeSH
- vakcinace metody MeSH
- vakcíny konjugované terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on the burden of invasive pneumococcal disease (IPD) and serotype distribution was examined across age groups from data collected by the Lebanese Inter-Hospital Pneumococcal Surveillance Program. METHODS: Between 2005 and 2020, 593 invasive Streptococcus pneumoniae isolates were collected from 79 hospitals throughout Lebanon. Serotypes and antimicrobial resistance (AMR) profiles were identified, and trends compared over 3 eras: PCV7, post-PCV7/ pre-PCV13, and PCV13 eras. RESULTS: The prevalence of PCV7 serotypes decreased significantly from 43.6% in the PCV7 era to 17.8% during the PCV13 era (p<0.001). PCV13-only serotypes remained stable in the PCV13 compared to the post-PCV7 eras, especially serotypes 1 and 3, whereas non-vaccine types (NVT) increased throughout the study period, especially 24 and 16F. The mortality rate increased substantially from 12.5% (PCV7 era) to 24.8% (PCV13 era). A significant decrease in AMR was observed across the three study eras. CONCLUSION: PCVs substantially impacted IPD and AMR in vaccinated and unvaccinated populations despite an increase in mortality driven by NVT. Broadening the recommendation of vaccination to include older age-groups, using higher valency vaccines, and implementing stringent antimicrobial stewardship are likely to further impact the burden of IPD.
- MeSH
- heptavalentní konjugovaná pneumokoková vakcína MeSH
- incidence MeSH
- kojenec MeSH
- lidé MeSH
- pneumokokové infekce * epidemiologie prevence a kontrola MeSH
- pneumokokové vakcíny MeSH
- séroskupina MeSH
- Streptococcus pneumoniae MeSH
- vakcinace MeSH
- vakcíny konjugované MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Libanon MeSH
BACKGROUND: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet). METHODS: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose. RESULTS: The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively. CONCLUSIONS: PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.
- MeSH
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- očkovací schéma MeSH
- pneumokokové infekce * epidemiologie prevence a kontrola MeSH
- pneumokokové vakcíny MeSH
- séroskupina MeSH
- Streptococcus pneumoniae * MeSH
- vakcíny konjugované MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
