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

This phase 2, randomized, open-label study assessed the immunogenicity and safety of an investigational meningococcal ABCWY vaccine (MenABCWY) that contains components of licensed vaccines against meningococcal serogroup B (4CMenB) and serogroups ACWY (MenACWY). A total of 500 healthy 10- to 25-year-old participants were randomly assigned to one of five study groups in a 1:1:1:1:1 ratio. Four groups received two doses 2 months apart of MenABCWY and 4CMenB plus MenACWY administered concomitantly in the same arm (4CMenB+ACWY/S group) or different arms (4CMenB+ACWY/D group) or 4CMenB administered alone. A fifth group received a single MenACWY dose. Immunogenicity was determined by serum bactericidal assay using human complement (hSBA). The study was powered to assess immunological interference against pooled serogroup B test strains. One month after the second vaccine dose, hSBA geometric mean titers (GMTs) (with 80% confidence intervals [CI]) against pooled serogroup B strains were 31.84 (80% CI, 28.18 to 35.98), 38.48 (80% CI, 34.23 to 43.26), 40.08 (80% CI, 35.44 to 45.33), and 42.38 (80% CI, 37.31 to 48.13) in the MenABCWY, 4CMenB+ACWY/S, 4CMenB+ACWY/D, and 4CMenB groups, respectively. Immune responses (GMTs and 80% CIs) were lower for PorA and NHBA serogroup B test strains in the MenABCWY group compared to the 4CMenB+ACWY/D group and 4CMenB group. Evaluation of solicited and unsolicited adverse events (AEs) identified no safety concerns for the MenABCWY vaccine. One serious AE (syncope in the 4CMenB group) was considered related to vaccination. In conclusion, there is no evidence of substantial immunological interference between 4CMenB and MenACWY vaccine components against serogroup B. The safety and tolerability profile of the investigational MenABCWY vaccine was acceptable. (This study has been registered at ClinicalTrials.gov under registration no. NCT03587207.) IMPORTANCE The bacterial species Neisseria meningitidis is a major cause of meningitis, with six meningococcal groups (serogroups) causing most cases. A licensed vaccine, MenACWY (Menveo), targets four of these meningococcal serogroups, and another vaccine, 4CMenB (Bexsero), targets serogroup B. A combined vaccine (MenABCWY) that targets all five serogroups is under development to simplify the vaccination schedule. In a previous study, the immune response to serogroup B was found to be overall higher in individuals who received 4CMenB than in those who received an investigational MenABCWY vaccine. We investigated this further by giving healthy adolescents and young adults the MenABCWY vaccine, 4CMenB plus MenACWY vaccine in the same or different arms, 4CMenB vaccine alone, or MenACWY vaccine alone. Immunogenicity results for serogroup B across study groups suggest no major interference between the MenB and MenACWY vaccine components. This supports further development of the combined MenABCWY vaccine.

• MeSH
• baktericidní aktivita krve MeSH
• dítě MeSH
• léky zkušební aplikace a dávkování   škodlivé účinky   MeSH
• lidé MeSH
• meningokokové vakcíny aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nežádoucí účinky léčiv epidemiologie   patologie   MeSH
• séroskupina MeSH
• vakcíny konjugované aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM197-conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent). METHODS: In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM197-conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12-15 months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2 μg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed. RESULTS: 951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2 µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded. CONCLUSION: Addition of 19A and 6A CRM197-conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV. Clinical trial registry: NCT01204658.

• MeSH
• bakteriální proteiny genetika   imunologie   MeSH
• Haemophilus influenzae MeSH
• imunogenicita vakcíny * MeSH
• imunoglobulin D genetika   imunologie   MeSH
• kojenec MeSH
• kombinované vakcíny aplikace a dávkování   MeSH
• lidé MeSH
• lipoproteiny genetika   imunologie   MeSH
• pneumokokové infekce imunologie   prevence a kontrola   MeSH
• pneumokokové vakcíny škodlivé účinky   imunologie   MeSH
• poliovirová vakcína inaktivovaná aplikace a dávkování   MeSH
• protilátky bakteriální krev   MeSH
• sekundární imunizace MeSH
• séroskupina MeSH
• Streptococcus pneumoniae MeSH
• transportní proteiny genetika   imunologie   MeSH
• vakcína proti diftérii, tetanu a pertusi aplikace a dávkování   MeSH
• vakcína proti hepatitidě B aplikace a dávkování   MeSH
• vakcíny konjugované škodlivé účinky   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
• 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

Přestože první pneumokokové celobuněčné očkovací látky byly vyvinuty již počátkem 20. století, konjugované vakcíny, které jsou účinné u kojenců a batolat mladších 2 let, byly do klinické praxe uvedeny až v roce 2000. V současné době je k dispozici 10valentní vakcína Synflorix a 13valentní vakcína Prevenar 13. Desetivalentní pneumokoková konjugovaná vakcína obsahuje polysacharidové antigeny sérotypů 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F a 23F, z nichž osm je konjugováno k proteinu D H. influenzae a sérotypy 18C a 19F k tetanickému a difterickému toxoidu. Vakcína je indikována k aktivní imunizaci proti invazivním pneumokokovým onemocněním, pneumonii a akutnímu zánětu středouší, které jsou vyvolány sérotypy zastoupenými ve vakcíně, u dětí od 6 týdnů do 5 let věku. Předregistrační studie byly založeny na hodnocení protilátkové odpovědi a jejím srovnání s užívanou 7valentní vakcínou. Předkládaný přehledový článek uvádí výsledky klinických randomizovaných kontrolovaných studií (FinIP, COMPAS) a neintervenčních studií z postmarketingového sledování. Publikovaná data potvrzují, že vakcína je účinná nejen v prevenci závažných invazivních pneumokokových onemocnění, ale i podstatně častějších slizničních infekcí, jakými jsou akutní otitida či pneumonie. Vakcína má velmi dobrý bezpečnostní profil a četnost lokálních i systémových reakcí po její aplikaci se významněji neodlišuje od jiných pneumokokových vakcín.

Pneumococcal whole-cell vaccines have been developed in the early 1900s, however, pneumococcal conjugated vaccines (PCV), which are effective in infants and children under two years of age, have been introduced in 2000. There are two PCVs available: a 10-valent (Synflorix) and a 13-valent vaccine (Prevenar 13). The 10-valent pneumococcal conjugated vaccine (PHiD-CV) includes polysaccharide antigens of the following serotypes: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F; eight of which are conjugated to protein D of H. influenzae and serotypes 18C and 19F are conjugated to tetanus or diphtheria toxoids. PHiD-CV is approved for active immunization against invasive pneumococcal diseases, pneumonia and acute otitis media caused by serotypes of S. pneumoniae included in the vaccine in children from 6 weeks to 5 years of age. Pre-licensure studies evaluated immune response to the vaccine and compared its immunogenicity with PCV7. This review includes the results of recently published clinical randomized controlled trials (FinIP, COMPAS) and non-interventional post-marketing studies. Published data confirm that PHiD-CV is effective in prevention of either severe invasive pneumococcal diseases or frequent superficial respiratory infections such as acute otitis media and pneumonia. The vaccine has a very good safety profile and incidence of local or systemic reactions after its administration is similar to other pneumococcal vaccines.

• Klíčová slova
• Desetivalentní pneumokoková konjugovaná vakcína (Synflorix),
• MeSH
• klinické zkoušky jako téma * MeSH
• lidé MeSH
• otitida diagnóza   etiologie   prevence a kontrola   MeSH
• pneumokokové infekce prevence a kontrola   MeSH
• pneumokokové vakcíny * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• pneumonie pneumokoková prevence a kontrola   MeSH
• statistika jako téma MeSH
• Streptococcus pneumoniae izolace a purifikace   patogenita   MeSH
• vakcíny konjugované * škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• hodnocení rizik MeSH
• hostitel s imunodeficiencí účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pneumokokové infekce * epidemiologie   komplikace   prevence a kontrola   MeSH
• pneumokokové vakcíny * imunologie   škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• vakcíny konjugované imunologie   škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• novinové články MeSH

• Klíčová slova
• Pneumo23 (PPV23), Prevenar13 (PCV13),
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• morbidita MeSH
• očkovací programy MeSH
• očkovací schéma MeSH
• pneumokokové infekce * epidemiologie   mortalita   prevence a kontrola   MeSH
• pneumokokové vakcíny * aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• pneumonie pneumokoková prevence a kontrola   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sérotypizace MeSH
• Streptococcus pneumoniae klasifikace   MeSH
• vakcinace metody   MeSH
• vakcíny konjugované * aplikace a dávkování   imunologie   škodlivé účinky   MeSH
• věkové rozložení MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: To provide broader protection against pneumococcal disease, new vaccines containing conserved Streptococcus pneumoniae proteins are being developed. This study assessed the safety, reactogenicity and immunogenicity of four formulations containing pneumococcal proteins pneumolysin toxoid (dPly) and histidine triad protein (PhtD) in toddlers. METHODS: In this phase II, multicenter, observer-blind study (www.clinicaltrials.gov: NCT00985751) conducted in the Czech Republic, toddlers (12-23 months) were randomized (1:1:1:1:1) to receive one of four investigational vaccine formulations (10 or 30μg each of dPly and PhtD, alone or in combination with polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine [PHiD-CV]), or the licensed PHiD-CV, in a 2-dose primary series plus booster at study months 0, 2 and 6. Solicited local and general symptoms were recorded within seven days post-vaccination, unsolicited symptoms within 31 days post-vaccination, and serious adverse events (SAEs) during the entire study period. Antibody concentrations against the vaccine components were measured pre-vaccination, one month post-dose 2, pre- and one month post-booster. RESULTS: 257 toddlers were enrolled and vaccinated. Percentages of solicited local and general symptoms following the different investigational formulations were generally within the same ranges as for PHiD-CV. After each dose, grade 3 fever (>40.0°C, rectal measurement) was reported for maximum one toddler in each group with no differences between investigational formulations and PHiD-CV during primary vaccination. 23 SAEs were reported for 17 toddlers, with distribution balanced between all groups except the group receiving 30 μg dPly/PhtD with PHiD-CV-conjugates (no SAEs reported). None of the SAEs were considered to be vaccine-related. For all pneumococcal protein-containing formulations, anti-PhtD and anti-Ply antibody geometric mean concentrations increased from pre-vaccination to post-dose 2 and from pre- to post-booster vaccination. CONCLUSION: All investigational vaccine formulations were well-tolerated and immunogenic when administered to toddlers as a 2-dose primary vaccination followed by a booster dose.

• MeSH
• bakteriální proteiny imunologie   MeSH
• hydrolasy imunologie   MeSH
• kojenec MeSH
• léky zkušební * MeSH
• lidé MeSH
• pneumokokové vakcíny aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• protilátky bakteriální krev   MeSH
• sekundární imunizace MeSH
• streptolysiny imunologie   MeSH
• vakcíny konjugované aplikace a dávkování   škodlivé účinky   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
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Prophylactic paracetamol (PP) was previously shown to reduce primary and booster antibody responses against the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). This study further evaluated the effect of PP on antibody persistence, immunological memory and nasopharyngeal carriage (NPC). METHODS: Two hundred and twenty children previously primed (3 doses, NCT00370318) and boosted (NCT00496015) with PHiD-CV with (PP group) or without (NPP group) prophylactic paracetamol administration received one PHiD-CV dose in their fourth year of life to assess the induction of immunological memory following previous immunisations. A control group of age-matched unprimed children enrolled in study NCT00496015 received an investigational tetravalent Neisseria meningitidis serogroups A, C, W-135, Y tetanus toxoid-conjugate vaccine, and thus remained unprimed for pneumococcal vaccination. Of these, 223 unprimed children received in the present study at least one PHiD-CV dose of a 2-dose catch-up regimen, which was relevant as control for assessment of immunological memory in PHiD-CV primed children. RESULTS: Induction of immunological memory was shown irrespective of PP administration at primary and booster vaccination. Antibody geometric mean concentrations were lower in the PP group for serotypes 1, 4, 7F and 9V. Opsonophagocytic titres did not differ significantly between PP and NPP groups. Previous use of PP seemed to have only a minor impact on kinetics of antibody persistence. Reduced NPC of vaccine pneumococcal serotypes and trends towards increased NPC of non-vaccine and non-cross-reactive serotypes were seen in primed groups versus the control group, with no obvious differences between PP and NPP groups. CONCLUSION: Regardless of whether previous PHiD-CV vaccination was given with or without PP, induction of immunological memory and persistence of PHiD-CV's impact on carriage was seen until at least 28 months post-booster vaccination. Our study results therefore suggest that the lower immune responses after primary and booster vaccination with PP are of transient nature.

• MeSH
• bakteriální proteiny imunologie   MeSH
• Haemophilus influenzae chemie   imunologie   MeSH
• imunologická paměť imunologie   MeSH
• lidé MeSH
• nazofarynx imunologie   MeSH
• paracetamol aplikace a dávkování   MeSH
• pneumokokové infekce imunologie   prevence a kontrola   MeSH
• pneumokokové vakcíny aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• předškolní dítě MeSH
• protilátky bakteriální imunologie   MeSH
• sekundární imunizace * MeSH
• vakcinace MeSH
• vakcíny konjugované aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• práce podpořená grantem MeSH

• MeSH
• alergie etiologie   prevence a kontrola   MeSH
• dítě MeSH
• informovaný souhlas u nezletilých zákonodárství a právo   MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• očkovací schéma MeSH
• vakcinace * psychologie   trendy   využití   zákonodárství a právo   MeSH
• vakcíny konjugované aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• vakcíny aplikace a dávkování   kontraindikace   škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH