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Markus Knuf,
Olivier Romain,
Klaus Kindler,
Uta Walther,
Phu-My Tran,
Heidemarie Pankow-Culot,
Thomas Fischbach,
Dorothee Kieninger-Baum,
Véronique Bianco,
Yaela Baine,
Jacqueline Miller
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ABSTRACT: In Europe, the introduction of monovalent meningococcal serogroup C (MenC) conjugate vaccines has resulted in a significant decline in MenC invasive disease. However, given the potential for strain evolution and increasing travel to areas of high endemicity, protection against additional serogroups is needed. In this study, the immunogenicity, measured by a serum bactericidal activity assay using rabbit complement (rSBA), and the safety of a quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) were compared to that of a licensed monovalent MenC conjugate vaccine (MenC-CRM(197)) in children 2-10 years of age. Children were randomised (3:1) to receive a single dose of either MenACWY-TT or MenC-CRM(197). Non-inferiority of the immunogenicity of MenACWY-TT versus MenC-CRM(197) in terms of rSBA-MenC vaccine response was demonstrated. Exploratory analyses suggested that rSBA-MenC geometric mean titres adjusted for pre-vaccination titres were lower in children vaccinated with MenACWY-TT compared to MenC-CRM(197). Nevertheless, at 1 month post-vaccination, ≥99.3 % of the children who received MenACWY-TT had rSBA titres ≥1:128 for each of the four vaccine serogroups, which is the more conservative correlate of protection. The reactogenicity and safety profile of MenACWY-TT was clinically acceptable and no serious adverse events considered related to vaccination were reported throughout the study. Conclusion: When administered to European school-age children, MenACWY-TT has a clinically acceptable safety profile and, when compared with MenC-CRM(197), the potential to broaden protection against meningococcal disease caused by serogroups A, W-135 and Y while maintaining protection against MenC. This study has been registered at www.clinicaltrials.gov NCT00674583.
European Journal of Pediatrics 01/2013; · 1.88 Impact Factor
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ABSTRACT: The present extension study, conducted in children originally vaccinated at 12-14 mo or 3-5 y of age, assessed antibody persistence and immune memory induced by an investigational tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT). In the original study, participants were randomized to receive one dose of MenACWY-TT or licensed age-appropriate meningococcal control vaccines. Fifteen months post-vaccination, all participants underwent serum sampling to evaluate antibody persistence and participants previously vaccinated as toddlers received a polysaccharide challenge to assess immune memory development. Exploratory comparisons showed that (1) All children and ≥ 92.3% of the toddlers maintained serum bactericidal (rSBA) titers ≥ 1:8 at 15 mo post MenACWY-TT vaccination; statistically significantly higher rSBA geometric mean titers (GMTs) were observed compared with control vaccines. (2) At one month after polysaccharide challenge, all toddlers primed with MenACWY-TT or with the monovalent serogroup C conjugate vaccine had rSBA titers ≥ 1:8 and ≥ 1:128 for serogroup C and similar rSBA-GMTs; rSBA-GMTs for serogroups A, W-135 and Y were statistically significantly higher in toddlers primed with MenACWY-TT compared with the control vaccine. Thus, a single dose of MenACWY-TT induced persisting antibodies in toddlers and children and immune memory in toddlers. This study has been registered at www.clinicaltrials.gov NCT00126984.
Human vaccines & immunotherapeutics. 07/2012; 8(7):866-72.
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ABSTRACT: Nine randomized controlled clinical trials, including approximately 26,000 children aged 6 months to 17 years, have evaluated the efficacy of live attenuated influenza vaccine (LAIV) against culture-confirmed influenza illness compared with placebo or trivalent inactivated influenza vaccine (TIV). The objective of the current analysis was to integrate available LAIV efficacy data in children aged 2-17 years, the group for whom LAIV is approved for use.
A meta-analysis was conducted using all available randomized controlled trials and a fixed-effects model. Cases caused by drifted influenza B were analyzed as originally classified and with all antigenic variants classified as dissimilar.
Five placebo-controlled trials (4 were 2-season trials) and 3 single-season TIV-controlled trials were analyzed. Compared with placebo, year 1 efficacy of 2 doses of LAIV was 83% (95% CI: 78, 87) against antigenically similar strains; efficacy was 87% (95% CI: 78, 93), 86% (95% CI: 79, 91), and 76% (95% CI: 63, 84) for A/H1N1, A/H3N2, and B, respectively. Classifying B variants as dissimilar, efficacy against all similar strains was 87% (95% CI: 83, 91) and 93% (95% CI: 83, 97) against similar B strains. Year 2 efficacy was 87% (95% CI: 82, 91) against similar strains. Compared with TIV, LAIV recipients experienced 44% (95% CI: 28, 56) and 48% (95% CI: 38, 57) fewer cases of influenza illness caused by similar strains and all strains, respectively. LAIV efficacy estimates for children from Europe, the United States, and Middle East were robust and were similar to or higher than those for the overall population.
In children aged 2-17 years, LAIV demonstrated high efficacy after 2 doses in year 1 and revaccination in year 2, and greater efficacy compared with TIV. This meta-analysis provides precise estimates of LAIV efficacy among the approved pediatric age group.
Vaccine 12/2011; 30(5):886-92. · 3.77 Impact Factor
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ABSTRACT: The hemagglutination inhibition (HI) titer of 1:40, which has been recognized as an immunologic correlate corresponding to a 50% reduction in the risk of contracting influenza, is based on studies in adults. Neither seasonal nor challenge-based correlates have been evaluated in children.
A total of 4707 influenza vaccine-naive healthy children 6 to 72 months old were randomized in a ratio of 2:2:1 to receive 2 doses of MF-59-adjuvanted influenza vaccine (Novartis Vaccines), trivalent inactivated influenza vaccine subunit (trivalent inactivated influenza vaccine control, GSK), or a saline placebo during the 2007 to 2008 and 2008 to 2009 influenza seasons. The second dose was given 30 days after dose 1. Clinical influenza-like illnesses cases identified by active surveillance were confirmed by reverse transcription polymerase chain reaction testing for influenza. Vaccine immunogenicity 50 days after dose 1 was evaluated in a subset of 777 children.
Immunogenicity and efficacy results for H3N2 were evaluated against the Prentice criteria, which confirmed that the immunogenicity results warranted estimation of an immunologic correlate. We then used the Dunning model fitting the H3N2 antibody titers at day 50 and the influenza cases observed in the immunogenicity subset to estimate a correlate of protection. This analysis revealed that a cutoff HI titer of 1:110 was associated with the conventional 50% clinical protection rate against infection during the entire season, and titers of 1:215, 1:330, and 1:629 predicated protection rates of 70%, 80%, and 90%, respectively. The conventional adult HI titer of 1:40 was only associated with 22% protection.
The use of the 1:40 HI adult correlate of protection is not appropriate when evaluating influenza vaccines in children. Although a cutoff of 1:110 may be used to predict the conventional 50% clinical protection rate, a titer of 1:330 would predict an 80% protective level, which would seem to be more desirable from a public health perspective.
The Pediatric Infectious Disease Journal 12/2011; 30(12):1081-5. · 3.58 Impact Factor
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ABSTRACT: The efficacy of inactivated influenza vaccines is known to be poor in infants and young children.
We studied the effect of the adjuvant MF59, an oil-in-water emulsion, on the efficacy of trivalent inactivated influenza vaccine (TIV) in 4707 healthy children 6 to less than 72 months of age who had not previously been vaccinated against influenza. The children were randomly assigned to three study groups, each of which received the assigned vaccines in two doses, 28 days apart, during two consecutive influenza seasons. Two of the groups were given age-appropriate doses of TIV either with or without the MF59 adjuvant, and the third group was given control (noninfluenza) vaccines to assess their absolute and relative efficacy against influenza-like illness, as confirmed by means of polymerase-chain-reaction (PCR) assay.
Attack rates of influenza-like illness across both influenza seasons were 0.7%, 2.8%, and 4.7% in the adjuvant, nonadjuvant, and control vaccine groups, respectively. The absolute vaccine efficacy rates against all influenza strains (94 of 110 cases were due to vaccine-matched H3N2 viruses) were 86% (95% confidence interval [CI], 74 to 93) for the MF59-adjuvant vaccine (ATIV) and 43% (95% CI, 15 to 61) for the vaccine without the adjuvant (TIV); the relative vaccine efficacy rate for ATIV versus TIV was 75% (95% CI, 55 to 87). The efficacy rates for ATIV were 79% (95% CI, 55 to 90) in children 6 to less than 36 months of age and 92% (95% CI, 77 to 97) in those 36 to less than 72 months of age, as compared with 40% (95% CI, -6 to 66) and 45% (95% CI, 6 to 68), respectively, for TIV. Antibody responses were higher with ATIV and remained so through day 181. The rates of systemic and local reactions to the influenza vaccines with and without the adjuvant were similar in the younger age group (relative risk, 1.04; 95% CI, 0.98 to 1.09), but systemic events in the older age group were more frequent after administration of ATIV (63%) than after administration of TIV (44%) or the control vaccine (50%). Serious adverse events were distributed evenly across the three vaccine groups.
Influenza vaccine with the MF59 adjuvant is efficacious against PCR-confirmed influenza in infants and young children. (Funded by Novartis Vaccines and Diagnostics; ClinicalTrials.gov number, NCT00644059.).
New England Journal of Medicine 10/2011; 365(15):1406-16. · 53.30 Impact Factor
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ABSTRACT: Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12-18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42-56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42-56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15-20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. CONCLUSION: Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211).
European Journal of Pediatrics 09/2011; 171(3):463-70. · 1.88 Impact Factor
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MMW Fortschritte der Medizin 09/2011; 153(37):46-7.
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Markus Knuf,
Heidemarie Pankow-Culot,
Detlef Grunert,
Michael Rapp,
Falko Panzer,
Ralph Köllges,
Aurélie Fanic,
Ahsan Habib,
Dorota Borys,
Ilse Dieussaert,
Lode Schuerman
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ABSTRACT: Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV).
Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured.
Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster.
Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.
The Pediatric Infectious Disease Journal 09/2011; 31(1):e31-6. · 3.58 Impact Factor
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ABSTRACT: The efficacy of vaccines against major encapsulated bacterial pathogens -Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b (Hib) - has been significantly enhanced by conjugating the respective polysaccharides with different carrier proteins: diphtheria toxoid; non-toxic cross-reactive material of diphtheria toxin(197), tetanus toxoid, N. meningitidis outer membrane protein, and non-typeable H. influenzae-derived protein D. Hib, meningococcal, and pneumococcal conjugate vaccines have shown good safety and immunogenicity profiles regardless of the carrier protein used, although data are conflicting as to which carrier protein is the most immunogenic. Coadministration of conjugate vaccines bearing the same carrier protein has the potential for inducing either positive or negative effects on vaccine immunogenicity (immune interference). Clinical studies on the coadministration of conjugate vaccines reveal conflicting data with respect to immune interference and vaccine efficacy.
Vaccine 05/2011; 29(31):4881-90. · 3.77 Impact Factor
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Markus Knuf,
Anna Pantazi-Chatzikonstantinou,
Ulrich Pfletschinger,
Irmingard Tichmann-Schumann,
Hartwig Maurer,
Lothar Maurer,
Thomas Fischbach,
Henrike Zinke,
Heidemarie Pankow-Culot,
Vassiliki Papaevangelou,
Veronique Bianco,
Marie Van der Wielen,
Jacqueline M Miller
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ABSTRACT: Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥ 97.3% of ACWY-TT vaccinees had rSBA titres ≥ 1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥ 98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.
Vaccine 03/2011; 29(25):4264-73. · 3.77 Impact Factor
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ABSTRACT: The rising incidence of pertussis amongst adults and adolescents in industrialized countries could be reduced by replacing tetanus and diphtheria (Td) boosters with reduced-antigen-content dT-acellular pertussis (dTpa)vaccines. Repeated administration of a dTpa-IPV (dTpa-inactivated poliomyelitis; BoostrixTM Polio, GlaxoSmithKline)booster to adolescents, 5 years after their previous dose was evaluated.
Before the second dTpa-IPV booster, the percentage of subjects who were seroprotected/seropositive was: 98.2% (D); 98.5% (T); 40.6% (PT); 99.7% (FHA); 97.0% (PRN); 98.8% (anti-polio 1); 99.7% (anti-polio 2); 97.0% (anti-polio 3). One month after the second dTpa-IPV dose, all subjects were seroprotected against D, T and polio and anti-pertussis booster responses (seroconversion or ≥2-fold increase) were seen in 93.3% (PT), 93.4% (FHA) and 95.2% (PRN) of subjects.During 4-day follow-up, 4.1% subjects recorded grade 3 pain; 4.6% and 3.6% recorded redness or swelling >50 mm, respectively. No serious adverse events were recorded. The incidence of symptoms was not higher than after the previous booster.
415 subjects (mean age 11.4 years) who had received either dTpa-IPV or dTpa + IPV at age 4–8 years, all received one dose of dTpa-IPV in this open, phase IV trial. Blood samples were taken before and one-month post-vaccination. Antibody concentrations against D, T, pertussis toxoid (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and polio antigens were determined. Reactogenicity and safety was assessed.
A second dTpa-IPV booster was highly immunogenic and well tolerated in this population of adolescents, supporting the repeated administration of BoostrixTM Polio. This study is registered at www.clinicaltrials.gov NCT00635128.
Human vaccines 07/2010; 6(7):554-61. · 3.58 Impact Factor
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ABSTRACT: After a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses.
The Journal of pediatrics 04/2010; 156(4):675-8. · 4.02 Impact Factor
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Markus Knuf,
Fred Zepp,
Claudius U Meyer,
Pirmin Habermehl,
Lothar Maurer,
Hanns-Michael Burow,
Ulrich Behre,
Michel Janssens,
Paul Willems,
Helmtrud Bisanz,
Volker Vetter,
Ruprecht Schmidt-Ott
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ABSTRACT: This study compared intramuscular and subcutaneous administration of two doses of measles-mumps-rubella-varicella (MMRV) combination vaccine (Priorix-Tetra, GlaxoSmithKline Biologicals) in children. Healthy children (N = 328) were randomised to receive MMRV either intramuscularly or subcutaneously. Reactogenicity was similar between treatment groups for immediate vaccination pain, vaccination site pain, redness and incidence of fever and rashes. Slightly less vaccination site swelling occurred during days 0-3 of the post-vaccination period after intramuscular administration. Seroconversion rates for all components, 42-56 days post-dose 2, ranged from 99.3% to 100% in the intramuscular group and from 98.6% to 100% in the subcutaneous. Cell-mediated immunity data supported the humoral immunogenicity findings. In summary, the MMRV vaccine is well tolerated and highly immunogenic when administered either subcutaneously or intramuscularly to children in the second year of life.
European Journal of Pediatrics 02/2010; 169(8):925-33. · 1.88 Impact Factor
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ABSTRACT: There is ongoing discussion as to whether it is beneficial to avoid pulmonary sinus augmentation in the arterial switch operation. We report a single-surgeon series of mid-term results for direct pulmonary artery anastomosis during switch operation for transposition of the great arteries (TGA).
This retrospective study includes 17 patients with TGA, combined with an atrial septal defect, patent foramen ovale or ventricular septal defect. Patient data was analyzed from hospital charts, including operative reports, post-operative course, and regular follow-up investigations. The protocol included cardiological examination by a single pediatric cardiologist. Echocardiographic examinations were performed immediately after arrival on the intensive unit, before discharge, and then after three, six, and 12 months, followed by yearly intervals. Pulmonary artery stenosis (PAS) was categorized into three groups according to the Doppler-measured pulmonary gradient: grade I (trivial stenosis) = increased pulmonary flow with a gradient below 25 mm Hg; grade II (moderate stenosis) = a gradient ranging from 25 to 49 mm Hg; and grade III (severe stenosis) = a gradient above 50 mm Hg. Follow-up data was available for all patients. The length of follow-up ranged from 1.2 to 9.7 years, median: 7.5 years (mean 6.1 years ± 14 months).
During follow-up, 12 patients (70.6%) had no (or only trivial) PAS, five patients (29.4%) had moderate stenosis without progress, and no patient had severe PAS. Cardiac catheterization after arterial switch operation was performed in 11 patients (64.7%) and showed a good correlation with echocardiographic findings. During follow-up there was no reintervention for PAS.
Direct reconstruction of the neo-pulmonary artery is a good option in TGA with antero-posterior position of the great vessels, with very satisfactory mid-term results.
Cardiology journal 01/2010; 17(6):574-9. · 1.31 Impact Factor
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ABSTRACT: The aim of our study was to facilitate perioperative calculation of potential risk factors on the outcome of corrective surgery for children with tetralogy of Fallot.
The medical records of 81 (44 female and 37 male) out of a total of 87 patients undergoing complete surgical repair of tetralogy of Fallot between 1988 and 2004 at the Children's Hospital of the Johannes Gutenberg University of Mainz were reviewed. PATIENTS were divided into four categories, depending on the severity of pulmonary stenosis and cyanosis, as well as on the type of pulmonary circulation.
Additional malformations did not affect mortality rates, but did directly affect the number of pleural effusions, time of epinephrine administration, duration of surgery, bypass, and ischemia, as well as length of hospitalization and intensive care unit treatment. In contrast to longer periods of extracorporeal circulation and ischemia during surgery, which are directly related not only to more complex anatomical situations but also to higher mortality and complication rates, the much-debated question of age at surgery had no influence either on the surgical approach itself or on the post-operative outcome.
Our patient categorization, and evaluation of potential pre-operative risk factors and intraoperative parameters, should prove useful for the future planning and execution of therapeutic procedures in institutions around the world.
Cardiology journal 01/2010; 17(1):20-8. · 1.31 Impact Factor
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ABSTRACT: Information on the onset of epidemics of acute respiratory tract infections (ARIs) is useful in timing preventive strategies (eg, the passive immunization of high-risk infants against respiratory syncytial virus [RSV]). Aiming at better predictions of the seasonal activity of ARI pathogens, we investigated the influence of climate on hospitalizations for ARIs.
Samples obtained from 3044 children hospitalized with ARIs in Mainz, Germany, were tested for pathogens with a multiplex reverse-transcriptase polymerase chain reaction enzyme-linked immunosorbent assay from 2001 through 2006. Hospitalizations for ARIs were correlated with meteorological parameters recorded at the University of Mainz. The frequency of hospitalization for RSV infection was predicted on the basis of multiple time series analysis.
Influenza A, RSV, and adenovirus were correlated with temperature and rhinovirus to relative humidity. In a time series model that included seasonal and climatic conditions, RSV-associated hospitalizations were predictable.
Seasonality of certain ARI pathogens can be explained by meteorological influences. The model presented herein is a first step toward predicting annual RSV epidemics using weather forecast data.
Clinical Infectious Diseases 09/2009; 49(6):861-8. · 9.15 Impact Factor
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ABSTRACT: Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised and critically ill patients. Standard culture based methods for the diagnosis of Aspergillus infections have limited sensitivity and specificity and are time consuming. The recent availability of novel molecular based diagnostic techniques offers the potential of rapid, highly sensitive and specific pathogen detection. In this study, we aimed to develop a diagnostic assay to detect simultaneously common pathogenic Aspergillus species including Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger and Aspergillus terreus in whole blood specimen. A real-time PCR/probe set assay was designed to amplify the 18sRNA genomic region of Aspergillus. In addition to a previously probe set validated for the detection of A. fumigatus ('Asp.fum'), two other probe sets ('Asp.ter'; 'Asp.nig') were synthesised with 100% sequence homology to A. terreus or A. niger. Specificity testing demonstrated amplification of Aspergillus DNA, but not DNA from a panel of other common pathogenic fungi and bacteria and/or human DNA. Sensitivity testing in serial dilution assays revealed a lower detection limit of 1-5 CFU ml(-1) whole blood. However, no single probe set was most sensitive for all Aspergillus species tested and a combination of all three probe sets was necessary to achieve maximal overall assay sensitivity. Furthermore, inclusion of a subsequent probe melting temperature (Tm) analysis demonstrated species-specific Tm-patterns, useful to differentiate simultaneously between the different Aspergillus species detected. We describe a highly specific and sensitive real-time PCR approach to detect and differentiate the most common pathogenic Aspergillus species in a rapid 'same day' assay.
Mycoses 05/2009; 52(3):228-33. · 2.25 Impact Factor
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ABSTRACT: Licensed pneumococcal conjugate vaccine (7vCRM) is usually coadministered with combination vaccines in pediatric immunization programs. Reactogenicity and safety after primary and booster vaccination with a novel 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in comparison with 7vCRM, both coadministered with commonly used pediatric vaccines, was evaluated in 5 clinical studies.
Five randomized, controlled studies in which PHiD-CV or licensed 7vCRM vaccines coadministered with various DTPa-based combination vaccines, Neisseria meningitidis serogroup C conjugate vaccines and DTPw-HBV/Hib were conducted. Local and general symptoms were solicited for 4 days after each vaccine dose, using diary cards. All adverse events were recorded for 31 days after each dose and serious adverse events throughout the entire study periods.
A total of 4004 subjects contributed to the safety data analyzed in this review. Fever >or=38.0 degrees C (rectal temperature) was reported after about one-third of primary or booster vaccine doses coadministered with DTPa-based vaccines and after approximately 60% of primary doses with DTPw coadministration in both PHiD-CV and 7vCRM groups. Fever >40.0 degrees C was reported after <or=1.1% of PHiD-CV doses and <or=2.2% of 7vCRM doses. The incidences and intensity of general reactions were generally within the same ranges in the PHiD-CV and 7vCRM groups. Drowsiness and irritability in the study with MenC-conjugates coadministration and irritability and loss of appetite in the study with DTPw-combined vaccines coadministration tended to be slightly higher in PHiD-CV groups. No such trend was observed for solicited general symptoms with grade 3 intensity.
The safety and reactogenicity profiles of PHiD-CV and 7vCRM were within the same range when administered for primary and booster vaccination in coadministration with other routinely used pediatric vaccines.
The Pediatric Infectious Disease Journal 05/2009; 28(4 Suppl):S109-18. · 3.58 Impact Factor
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ABSTRACT: Immunogenicity of the candidate 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was assessed when coadministered with other routine pediatric vaccines including different Neisseria meningitidis serogroup C conjugate vaccines.
One thousand five hundred forty-eight healthy infants received, according to a balanced (1:1:1:1) randomization, either PHiD-CV coadministered with (1) DTPa-HBV-IPV/Hib (Infanrix hexa) and MenC-CRM (Meningitec), (2) DTPa-HBV-IPV/Hib and MenC-TT (NeisVac-C), or (3) DTPa-HBV-IPV (Infanrix penta/Pediarix) and Hib-MenC-TT (Menitorix); or 7vCRM (Prevenar/Prevnar) coadministered with DTPa-HBV-IPV and Hib-MenC-TT at 2-4-6 months of age with a booster dose at 11-18 months. Serotype-specific pneumococcal responses were measured by 22F-inhibition ELISA and opsonophagocytic (OPA) assay.
In all 3 coadministration groups, PHiD-CV was immunogenic for each of the 10 pneumococcal vaccine serotypes as assessed by post-primary and post-booster antibody ELISA and OPA responses. When coadministered with DTPa-HBV-IPV, Hib, and MenC antigens, PHiD-CV responses after the third primary dose were within the same range as 7vCRM responses in terms of the percentage of subjects achieving an ELISA antibody concentration >or=0.2 microg/mL for all common vaccine serotypes (over 92% of subjects) except for serotype 6B (at least 87% of subjects). ELISA and OPA immune responses were also evident after the second primary doses of PHiD-CV or 7vCRM vaccine, although antibody levels were below that achieved after 3 primary doses, particularly for serotypes 6B and 23F. The kinetics of the immune responses from after the second dose to after the booster dose were similar for most of the serotypes in both PHiD-CV and 7vCRM groups.
PHiD-CV was immunogenic when coadministered with other routine pediatric vaccines including MenC conjugate vaccines.
The Pediatric Infectious Disease Journal 05/2009; 28(4 Suppl):S77-88. · 3.58 Impact Factor
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ABSTRACT: The choice of non-typeable Haemophilus influenzae Protein D as main carrier protein in the candidate 10-valent pneumococcal conjugate vaccine (PHiD-CV, GlaxoSmithKline Biologicals), was driven in part to avoid carrier-mediated suppression and possible bystander interference with coadministered vaccines. Immunogenicity data from 3 primary and 2 booster vaccination studies were assessed for possible impacts of PHiD-CV coadministration on immune responses to routinely administered childhood vaccines, in comparison to 7-valent pneumococcal conjugate vaccine (7vCRM) coadministration.
Randomized, controlled studies in which PHiD-CV or 7vCRM vaccines were coadministered with DTPa-[HBV]-IPV/Hib, DTPa-[HBV]-IPV, DTPw-HBV/Hib, IPV, and OPV, combined Hib-Neisseria meningitidis serogroup C vaccine (Hib-MenC-TT), standalone MenC-TT or MenC-CRM vaccines.
One month after primary vaccination, >96% of PHiD-CV recipients had seroprotective antibody concentrations against diphtheria, tetanus, poliovirus types 1 and 3, Hib (>or=0.15 microg/mL), SBA-MenC (>or=1:8), and >94% were seropositive for antibodies against pertussis antigens. Somewhat lower responses against poliovirus type 2 in study A (compared with poliovirus type 1 and 2 responses) and hepatitis B in the 6-, 10-, and 14-week schedule in the Philippines (compared with hepatitis B responses in the other studies) were observed after coadministration of both PHiD-CV and 7vCRM vaccines. Antitetanus and anti-PRP antibody geometric mean concentrations (GMCs) tended to be higher after PHiD-CV coadministration, probably because of the TT carrier protein for serotype 18C in PHiD-CV. Booster vaccination induced substantial increases in antibody GMCs for all coadministered antigens. These responses were generally within the same range in PHiD-CV and 7vCRM groups. Observed anti-PRP responses remained higher in PHiD-CV recipients after the booster dose.
Coadministration of PHiD-CV with commonly used childhood vaccines induced high levels of seroprotection/seropositivity against all targeted diseases. No evidence of negative interference on the immune response to any of the coadministered vaccine antigens was observed when compared with the current routine practice of 7vCRM coadministration.
The Pediatric Infectious Disease Journal 05/2009; 28(4 Suppl):S97-S108. · 3.58 Impact Factor
