[Show abstract][Hide abstract] ABSTRACT: The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed.
PLoS Medicine 06/2014; 11(6):e1001657. · 15.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a previous study, 3-dose primary vaccination of Nigerian infants with the 10-valent pneumococcal nontypeable Hemophilus influenzae protein D conjugate vaccine (PHiD-CV) was immunogenic for vaccine pneumococcal serotypes, with comparable tolerability between PHiD-CV and control groups. In an open-label study (ClinicalTrials.gov, NCT01153893), 68 primed children received a PHiD-CV booster dose co-administered with a diphtheria-tetanus-acellular pertussis (DTPa) booster dose at 15-21 months and 36 children unprimed for pneumococcal vaccination received two PHiD-CV catch-up doses (first dose co-administered with DTPa booster dose) at 15-21 and 17-23 months. Adverse events were recorded and immune responses were measured before and one month after vaccination. In both groups, pain was the most frequent solicited local symptom and fever was the most frequent solicited general symptom after the booster dose and each catch-up dose. Few grade 3 solicited symptoms and no vaccine-related serious adverse events were reported. After booster vaccination, for each vaccine serotype, at least 98.5% of children had an antibody concentration ≥0.2 µg/ml and at least 94.0% had an opsonophagocytic activity (OPA) titer ≥8. After 2-dose catch-up, for each vaccine serotype, at least 97.1% had an antibody concentration ≥0.2 µg/ml, except for serotypes 6B (82.9%) and 23F (88.6%), and at least 91.4% had an OPA titer ≥8, except for serotypes 6B (77.4%) and 19F (85.3%). PHiD-CV induced antibody responses against protein D in both groups. In conclusion, PHiD-CV administered to Nigerian toddlers as a booster dose or 2-dose catch-up was well tolerated and immunogenic for vaccine pneumococcal serotypes and protein D.
Human vaccines & immunotherapeutics. 12/2013; 10(3).
[Show abstract][Hide abstract] ABSTRACT: The immunogenicity, reactogenicity and safety of the 10- valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in a cohort of Nigerian infants included in a study conducted in Mali and Nigeria (ClinicalTrials.gov identifier: NCT00678301).
In this open, randomised, controlled study, 119 healthy infants received combined diphtheria-tetanus-whole-cell pertussis-hepatitis B/ Haemophilus influenzae type b vaccine (DTPw-HBV/Hib) and oral poliovirus vaccine (OPV) co-administered with PHiD-CV (PHiD-CV group) or without PHiD-CV (control group) at 6-10-14 weeks of age. Pneumococcal antibody responses and opsonophagocytic activity were measured and adverse events were recorded.
One month post-dose 3, for each of the vaccine pneumococcal serotypes, e"90.1% of PHiD-CV recipients had an antibody concentration e"0.2 ug/mL compared to < 9 % (except for serotypes 14 [32.4%] and 19F [27.8%]) in the control group. For each of the vaccine pneumococcal serotypes, e"90.6% of infants in the PHiD-CV group had an OPA titre e"8, compared to % 18% (except for serotype 7F [60.0%]) in the control group. Anti-protein D antibody geometric mean antibody concentrations were 2949.7 EL.U/mL in the PHiD-CV group and 68.9 EL.U/mL in the control group. For each DTPw-HBV/Hib antigen antibody seroprotection/seropositivity rates were e"94.4%. Tolerability was generally comparable between the PHiD-CV and control vaccination groups. Conclusions: PHiD-CV co-administered with routine vaccines was immunogenic for all vaccine pneumococcal serotypes and protein D in Nigerian infants. Vaccine tolerability was generally comparable between the PHiD-CV and control groups. These results suggest PHiD-CV can be co-administered with other vaccines included in the National Programme on Immunisation.
The Nigerian postgraduate medical journal 12/2013; 20(4):272-81.
[Show abstract][Hide abstract] ABSTRACT: Antimicrobial drugs are frequently prescribed to children for respiratory tract infections such as otitis, tonsillitis, sinusitis, and pneumonia. We assessed the effect of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; GlaxoSmithKline) on antimicrobial purchases.
In this nationwide phase 3-4 cluster-randomised, double-blind trial, children younger than 19 months were randomly assigned to receive PHiD-CV10 in 52 of 78 clusters or hepatitis B or A vaccine as control in 26 clusters according to three plus one or two plus one schedules (infants younger than 7 months) or catch-up schedules (children aged 7-18 months). The main objective for the antimicrobial treatment outcome was to assess vaccine effectiveness against outpatient prescriptions of antimicrobial drugs recommended by national treatment guidelines for acute otitis media in Finland in children who received at least one dose of study vaccine before 7 months of age. Masked follow-up lasted from the date of first vaccination (from Feb 18, 2009, through Oct 5, 2010) to Dec 31, 2011. We obtained data on all purchased antimicrobial prescriptions through the benefits register of the Social Insurance Institution of Finland. This and the nested acute otitis media trial are registered at ClinicalTrials.gov, numbers NCT00861380 and NCT00839254.
More than 47 000 children were enrolled. In 30 527 infants younger than 7 months at enrolment, 98 436 outpatient antimicrobial purchases were reported with incidence of 1·69 per person-year in the control clusters. Analysis of the main objective included 91% of all antimicrobial purchases: 31 982 in the control and 57 964 in the PHiD-CV10 clusters. Vaccine effectiveness was 8% (95% CI 1-14) and the incidence rate difference 0·12 per person-year corresponding to the number needed to vaccinate of five (95% CI 3-67) to prevent one purchase during the 2 year follow-up for combined PHiD-CV10 three plus one and two plus one infant schedules. The vaccine effectiveness was identical for the two infant schedules. In the catch-up schedules, the vaccine effectiveness was 3% (95% CI -4 to 10).
Despite low relative rate reductions the absolute rate reductions were substantial because of the high incidence of the outcome. This reduction would lead to over 12 000 fewer antimicrobial purchases per year in children younger than 24 months in Finland (birth cohort of 60 000 children).
GlaxoSmithKline Biologicals SA and National Institute for Health and Welfare (THL), Finland.
The Lancet Infectious Diseases 11/2013; · 19.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Background: Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was previously shown to be immunogenic and well tolerated in Malian children. Data on booster vaccination with a fourth consecutive dose of PHiD-CV are available for Europe, Asia and Latin America but are lacking for Africa. The present study evaluated further the safety, reactogenicity and immunogenicity of a fourth consecutive (booster) dose of PHiD-CV. Results: Low incidences of AEs with grade 3 intensity (2.1% of subjects) were observed. There were no reports of large swelling reactions and serious adverse events. One month post-booster vaccination, for each vaccine pneumococcal serotype, at least 97.8% of subjects had antibody concentrations ≥ 0.2 μg/ml, and at least 97.1% of subjects had opsonophagocytic activity ≥ 8. From pre- to post-booster, a 12.3-fold increase in anti-protein D geometric mean concentration was observed. Methods: This phase III, open-label study was conducted in Ouelessebougou, Mali, between November 2009 and June 2010. The study population consisted of Malian children previously primed (3 doses) with PHiD-CV in study NCT00678301 receiving a fourth consecutive (booster) dose of PHiD-CV in the second year of life. The incidences of adverse events (AEs) with grade 3 intensity (primary objective) or of any intensity (secondary objective), and the immunogenicity (secondary objective) of the PHiD-CV booster dose were assessed. Conclusion: A booster dose of PHiD-CV was well tolerated when administered to Malian children in the second year of life and was highly immunogenic for all 10 vaccine pneumococcal serotypes and NTHi protein D. (ClinicalTrials.gov identifier: NCT00985465).
Human vaccines & immunotherapeutics. 01/2013; 9(2).
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was designed to assess the effectiveness of a pneumococcal vaccine containing ten serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid as the carrier proteins (PHiD-CV10) against invasive pneumococcal disease. METHODS: In this cluster-randomised, double-blind trial, children aged younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants aged younger than 7 months at the first vaccination received either a 3+1 or a 2+1 vaccination schedule, children aged 7-11 months received a 2+1 schedule, and those 12-18 months of age received a two-dose schedule. The primary and secondary objectives were to assess vaccine effectiveness against culture-confirmed invasive pneumococcal disease due to any of the ten vaccine serotypes for the 3+1 and 2+1 schedules, respectively, in children who received at least one PHiD-CV10 dose before 7 months of age. Masked follow-up of pneumococcal disease lasted from the first vaccination (from February, 2009, to October, 2010) to January 31, 2012. Invasive disease data were retrieved from data accumulated in the national infectious diseases register. This trial and the nested acute otitis media trial are registered with ClinicalTrials.gov, numbers NCT00861380 and NCT00839254, respectively. FINDINGS: 47 369 children were enrolled from February, 2009, to October, 2010. 30 528 participants were assessed for the primary objective. 13 culture-confirmed vaccine-type cases of invasive pneumococcal disease were detected: none in the PHiD-CV10 3+1 group, one in the PHiD-CV10 2+1 group, and 12 in the control groups. The estimates for vaccine effectiveness were 100% (95% CI 83-100) for PHiD-CV10 3+1 and 92% (58-100) for PHiD-CV10 2+1 groups. Two cases of any culture-confirmed invasive disease irrespective of serotype were detected in combined PHiD-CV10 infant cohorts compared with 14 in the corresponding control cohorts (vaccine effectiveness 93%, 75-99). In catch-up cohorts, seven cases of invasive disease were reported, all in the control group: two cases in the children enrolled at 7-11 months of age; and five cases in children enrolled at 12-18 months of age (vaccine effectiveness 100%, 79-100). Non-fatal serious adverse events suspected to be vaccine-related were reported via routine post-immunisation safety surveillance in 18 children. INTERPRETATION: This nationwide trial showed high PHiD-CV10 effectiveness against invasive pneumococcal disease when given in different schedules. For the first time, effectiveness of a 2+1 schedule in infants was confirmed in a clinical trial. FUNDING: GlaxoSmithKline Biologicals SA and National Institute for Health and Welfare, Finland.
The Lancet 11/2012; 381(9862). · 39.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. This study evaluated the effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial colonization compared with the 7-valent pneumococcal conjugate vaccine (7vCRM) in young children.Methods. A randomized controlled trial in the Netherlands, initiated 2 years post-7vCRM introduction, was conducted between April 1, 2008 and December 1, 2010. Infants (n=780) received either PHiD-CV or 7vCRM (2:1) at 2, 3, 4 and 11-13 months of age. Nasopharyngeal samples taken at 5, 11, 14, 18 and 24 months of age were cultured to detect Haemophilus influenzae (Hi), Streptococcus pneumoniae (Spn), Moraxella catarrhalis (Mc) and Staphylococcus aureus (Sa). PCR assays quantified Hi and Spn and confirmed Hi as nontypeable (NTHi). Primary outcome measure was vaccine efficacy (VE) against NTHi colonization.Results. In both groups, NTHi colonization increased with age from 33% in 5-month-old to 65% in 24-month-old children. 3 months post-booster, VE against colonization was 0.5% (95% CI, -21.8% to 18.4%) and VE against acquisition 10.9% (95% CI, -31.3% to 38.9%). At each sampling moment, no differences between groups in either NTHi prevalence or Hi density were detected. Spn (range, 39%-57%), Mc (range, 63%-69%) and Sa (range, 9%-30%) colonization patterns were similar between groups.Conclusions. PHiD-CV had no differential effect on nasopharyngeal NTHi colonization or Hi density in healthy Dutch children up to two years of age, implying that herd effects for NTHi are not to be expected. Other bacterial colonization patterns were also similar.
[Show abstract][Hide abstract] ABSTRACT: The immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae (H. Influenzae) protein D conjugate vaccine (PHiD-CV), co-administered with routine childhood vaccines, were assessed in Taiwanese infants.
In this open study, 230 healthy infants were primed with three doses of PHiD-CV (Synflorix) and diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine (DTPa-HBV-IPV/Hib vaccine) at 1.5, 3 and 6 months of age and two doses of oral human rotavirus vaccine at 1.5 and 3 months. Pneumococcal immune responses were assessed 1 month post-dose three, by 22F-inhibition ELISA and opsonophagocytic activity (OPA) assay. Local and general solicited/unsolicited symptoms and serious adverse events (SAEs) were recorded.
At least 95.4% of participants had an antibody concentration ≥0.2 μg/mL against each vaccine serotype. At least 96.1% of participants had an OPA titer ≥8 against each vaccine serotype except 6B (87.3%). All infants, but one, were seropositive for antibodies against nontypeable H. influenzae protein D. Immune responses to the co-administered vaccines were good and in line with previous reports. PHiD-CV was well tolerated, with low (≤6.3%) incidences of grade 3 solicited local symptoms. The frequencies of general symptoms were in line with other pneumococcal conjugate vaccine studies. There were no systematic increases in incidences of solicited general or local symptoms with successive doses. There were no reports of grade 3 fever (rectal temperature > 40 °C) or SAEs considered to be causally related to vaccination.
PHiD-CV co-administered with routine childhood vaccines within the first 6 months of life, was highly immunogenic, and well tolerated in Taiwanese infants.
Journal of the Formosan Medical Association 09/2012; 111(9):495-503. · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In India, pneumococcal diseases are major causes of child mortality, and effective vaccines against Streptococcus pneumoniae are needed. This single-blind, randomized study assessed the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Hemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) co-administered with DTPw-HBV/Hib in Indian infants as 3-dose primary vaccination course. A total of 360 infants were randomized (2:1) to receive either PHiD-CV co-administered with DTPw-HBV/Hib (PHiD-CV group) or a Hib vaccine co-administered with DTPw-HBV (control group) at 6, 10, and 14 weeks of age. For each vaccine pneumococcal serotype, the percentage of infants in the PHiD-CV group with antibody concentrations ≥ 0.2 µg/mL one month after the third vaccine dose was at least 98.3%, except for serotypes 6B (77.7%) and 23F (89.5%), and opsonophagocytic activity titers ≥ 8 were measured in at least 95.7% of infants, except for serotypes 1 (90.5%) and 6B (84.5%). In addition, all the infants in the PHiD-CV group were seroprotected against diphtheria, tetanus, Hib, and hepatitis B or seropositive for antibodies against pertussis and NTHi protein D (except one infant). Incidences of solicited local and general symptoms were comparable between groups, except for fever (axillary temperature ≥ 37.5°C), which seemed to occur more frequently in the PHiD-CV group. In conclusion, PHiD-CV was shown to be immunogenic and well-tolerated when co-administered with DTPw-HBV/Hib in Indian infants.
Human vaccines & immunotherapeutics. 05/2012; 8(5):612-22.
[Show abstract][Hide abstract] ABSTRACT: We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 μg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 μg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines.
[Show abstract][Hide abstract] ABSTRACT: Pneumonia is still the leading cause of death among children in Africa, and pneumococcal serotypes 1 and 5 are frequently isolated from African children with invasive pneumococcal disease below the age of 5 years. The immunogenicity, safety and reactogenicity of 3-dose primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in infants in Mali and Nigeria.
In an open, randomized, controlled study, 357 infants received DTPw-HBV/Hib and OPV primary vaccination with (PHiD-CV group) or without (control group) PHiD-CV co-administration at 6, 10 and 14 weeks of age. Pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured and adverse events (AEs) recorded.
One month post-dose 3, ≥ 97.2% of PHiD-CV-vaccinated infants had an antibody concentration ≥ 0.2 μg/mL for each vaccine pneumococcal serotype except for 6B (82.0%) and 23F (87.6%) versus < 10% in the control group except for serotypes 14 (35.7%) and 19F (22.5%). For each vaccine serotype, ≥ 93.3% of PHiD-CV recipients had an OPA titre ≥ 8, except for serotypes 1 (87.6%) and 6B (85.4%), compared to < 10% in the control group, except for serotypes 7F (42.9%), 9V (24.1%) and 14 (24.5%). Anti-protein D geometric mean antibody concentrations were 3791.8 and 85.4 EL.U/mL in the PHiD-CV and control groups, respectively. Overall incidences of solicited and unsolicited AEs were similar between groups.
In sub-Saharan African infants, PHiD-CV was immunogenic for all vaccine pneumococcal serotypes and protein D. Vaccine tolerability was generally comparable between the PHiD-CV and control groups.
ClinicalTrials.gov identifier: NCT00678301.
BMC Public Health 11/2011; 11:882. · 2.32 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: The immunogenicity and safety of the 10-valent pneumococcal conjugate vaccine, PHiD-CV, have been documented in European and Asian studies. In this open study conducted in Mexico (NCT00489554), 230 healthy infants received three doses of PHiD-CV and DTPa-HBV-IPV/Hib vaccines at 2, 4 and 6 months of age and two doses of oral human rotavirus vaccine at 2 and 4 months. Serotype-specific pneumococcal responses and opsonophagocytic activity (OPA) were measured one month post-dose 3. PHiD-CV's primary vaccination course was highly immunogenic against each of the 10 pneumococcal vaccine serotypes and carrier protein D. Antibody responses against pneumococcal serotypes and protein D were generally higher in Mexican infants compared with European antibody responses, and functional OPA responses were also higher or in the same range. The most frequent solicited local symptom was pain, with high but similar incidences of grade 3 pain reported at both injection sites (up to 15% of all doses). PHiD-CV was well tolerated, with no serious adverse events considered as causally related to vaccination. Most solicited symptoms were mild and there was no increase in incidence of solicited symptoms with successive vaccine doses.
Human vaccines 11/2011; 7(11):1137-45. · 3.14 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: This randomized single-blind study in Korea evaluated noninferiority of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) versus the 7-valent pneumococcal conjugate vaccine (7vCRM) when both were coadministered with H. influenzae type b (Hib) conjugate vaccine, as opposed to coadministration with diphtheria-tetanus-acellular pertussis-based combination vaccines in previous studies.
Infants received 3 primary doses at 2, 4, and 6 months and a booster dose at 12 to 18 months of PHiD-CV (N = 374) or 7vCRM (N = 129), both coadministered with Hib vaccine. Immune responses were measured 1 month postdose 3 and postbooster using 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity assay.
PHiD-CV-induced antibody responses against each of the vaccine pneumococcal serotypes and protein D. Noninferiority to 7vCRM was demonstrated for all 10 PHiD-CV serotypes in terms of percentages of subjects reaching an antibody concentration ≥0.2 μg/mL after primary vaccination. Postprimary and postbooster, percentages of subjects with antibody concentration ≥0.2 μg/mL or opsonophagocytic activity titer ≥8 were generally consistent between groups for each pneumococcal serotype common to both vaccines. The safety and reactogenicity profiles of PHiD-CV and 7vCRM were generally comparable after both primary and booster vaccination.
In this Korean study, 3-dose PHiD-CV priming followed by a booster dose was immunogenic for all 10 vaccine pneumococcal serotypes and protein D. Noninferiority to 7vCRM in terms of enzyme-linked immunosorbent assay threshold responses postpriming was demonstrated. The safety and reactogenicity profiles of both vaccines when coadministered with Hib vaccine were generally comparable.
[Show abstract][Hide abstract] ABSTRACT: The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in preterm infants were assessed in this study.
Three parallel groups of infants received 3-dose primary immunization with PHiD-CV at 2, 4, and 6 months of age and a booster dose at 16 to 18 months: preterm I (gestation period ≥ 27 and <31 weeks, N = 50); preterm II (≥31 and <37 weeks, N = 87); and term (≥37 weeks, N = 149). Solicited symptoms and adverse events were recorded. Immune responses to PHiD-CV and coadministered vaccine antigens were measured.
The incidence of solicited general symptoms was similar across groups, and the frequency of grade 3 general symptoms was low. Incidences of redness and swelling were generally lower in preterm infants. PHiD-CV was immunogenic for each of the 10 vaccine pneumococcal serotypes (postprimary, ≥92.7% of infants reached enzyme-linked immunosorbent assay antibody concentrations ≥ 0.2 μg/mL and postbooster, ≥97.6%) and for protein D, with a trend for lower postprimary geometric mean antibody concentrations and opsonophagocytic activity (OPA) titers in preterm infants for some pneumococcal serotypes. Postbooster, ≥91.9% of subjects in each group had an OPA titer ≥ 8 for each of the vaccine serotypes. Pneumococcal antibody concentrations and OPA titers after priming and booster vaccination were comparable between the 2 preterm groups.
PHiD-CV was well tolerated and immunogenic in preterm infants when given as a 3-dose primary vaccination, with robust enzyme-linked immunosorbent assay antibody and OPA booster responses in the second year of life.
[Show abstract][Hide abstract] ABSTRACT: Immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein d conjugate vaccine (PHiD-CV), administered as 2-dose or 3-dose priming followed by a booster dose, has been described previously. The present study evaluated immunologic memory following PHiD-CV vaccination according to these vaccination schedules.
A dose of PHiD-CV (to test anamnestic responses) was administered to 172 children at 36 to 46 months of age; 110 of them had previously been vaccinated with PHiD-CV according to 2 + 1 or 3 + 1 schedules (PHiD-CV [2 + 1] and PHiD-CV [3 + 1] groups) and 62 were unprimed age-matched controls. To measure immune responses before and 7 to 10 days after the PHiD-CV dose, 22F-inhibition enzyme-linked immunosorbent assay and opsonophagocytic activity (OPA) assay were used.
Serotype-specific IgG geometric mean concentrations (GMCs) and OPA geometric mean titers increased substantially (from before to 7 to 10 days after the additional PHiD-CV dose) for all 10 vaccines and 2 cross-reactive serotypes (6A and 19A) in the children previously vaccinated with PHiD-CV, regardless of the vaccination schedule used. Antibody GMCs and OPA geometric mean titers after the administration of the PHiD-CV dose were markedly higher in both previously PHiD-CV-vaccinated groups than in the unprimed control group, clearly demonstrating prior induction of immunologic memory. Antiprotein D antibody GMCs had also increased substantially from before to 7 to 10 days after vaccination in all 3 groups, with higher antibody GMCs in the previously vaccinated groups than in the control group.
PHiD-CV vaccination according to 2 + 1 or 3 + 1 schedules resulted in comparable anamnestic immune responses. These findings suggest that similar protective efficacy may be achieved with both the schedules.
[Show abstract][Hide abstract] ABSTRACT: We evaluated catch-up vaccination schedules with 10-valent pneumococcal nontypeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV).
In this open, controlled study, children stratified into 4 age groups (N = 150 each) were vaccinated with PHiD-CV: (a) <6 months reference group: 3 primary doses with booster at 12 to 15 months, (b) 7 to 11 months: 2 doses and booster at 12 to 15 months, (c) 12 to 23 months: 2 doses, and (d) 2 to 5 years: 1 dose. Serotype-specific pneumococcal responses were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic activity (OPA) assay.
In the 7 to 11 months group postbooster antibody geometric mean concentrations (except for 2 serotypes) and OPA geometric mean titers (GMTs) were in the same ranges or higher relative to postbooster values in the <6 months reference group. Following 2 doses in the 12 to 23 months group, the percentages reaching threshold levels for ELISA (except for serotypes 6B and 23F) and OPA (except for serotype 1) were comparable or higher than <6 months reference postbooster values. Antibody geometric mean concentrations and OPA GMTs, while comparable or higher than reference postprimary values, were for some serotypes lower than reference postbooster values. Following 1 dose in the 2 to 5 years group ELISA responses were lower than the reference group for several serotypes.
A catch-up PHiD-CV schedule of 2 doses and booster for children 7 to 11 months of age was acceptable. For children 12 to 23 months of age, 2 doses seem to provide adequate priming although a booster dose might confer further benefit. Responses following 1 dose in children 2 to 5 years of age suggest that 2 doses may be preferable.
[Show abstract][Hide abstract] ABSTRACT: The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™) were assessed in 240 healthy Chilean children randomized to receive 3 doses of PHiD-CV (PHiD-CV group) or hepatitis A vaccine (HAV control group) at 2-4-6 months of age. All were offered 1 HAV dose at 12 months (outside study). The PHiD-CV group received a second HAV dose at 18-21 months and PHiD-CV booster at 20-23 months. The HAV control group received 2 PHiD-CV catch-up doses at 18-21 and 20-23 months. Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured. Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary, booster and catch-up doses was in line with previous PHiD-CV studies, although generally higher than with HAV. For each vaccine serotype, the percentage of subjects with antibody concentrations ≥0.2 µg/ml (GSK's 22F-inhibition ELISA) was at least 93.2% following 3 PHiD-CV primary doses and at least 97.4% post-booster; percentages with OPA titers ≥8 were at least 91.7% post-booster. After 2-dose catch-up, at least 94.3% of children had antibody concentrations ≥0.2 µg/ml against each serotype except 6B (84.3%); at least 95.2% had OPA titers ≥8 except against serotypes 1, 5 and 6B. In conclusion, the safety profiles of 2 PHiD-CV vaccination schedules (3-dose primary plus booster and 2-dose catch-up) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein D.
Human vaccines 05/2011; 7(5):511-22. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent reviews have highlighted the unpredictability of immunologic interference when multivalent conjugated vaccines are coadministered with other pediatric vaccines.
To evaluate immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix, GlaxoSmithKline Biologicals) and DTPa-IPV-Hib (Pediacel, Sanofi Pasteur MSD) when coadministered as a 3-dose primary vaccination course.
In a single-blind, single-center, randomized controlled trial in the Netherlands, healthy infants (n = 780) were randomly assigned (1:1:1) to receive either (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix Hexa, GlaxoSmithKline Biologicals), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (Prevenar/Prevnar, Pfizer Inc.) + DTPa-IPV-Hib at 2, 3, and 4 months of age. Blood samples were collected 1 month after dose 3. Diary cards were used to record safety and reactogenicity.
Antibody concentrations elicited by PHiD-CV coadministered with DTPa-IPV-Hib were noninferior to those following DTPa-HBV-IPV/Hib coadministration for 9 of 10 vaccines pneumococcal serotypes and protein D. For serotype 18C (conjugated to tetanus toxoid), the antibody concentration was higher with DTPa-HBV-IPV/Hib coadministration (1.73 vs. 1.07 μg/mL). The percentages of infants with antibody concentrations ≥0.2 μg/mL (68.9%-100% in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 64.9%-100% in the PHiD-CV + DTPa-IPV-Hib group) and with measurable opsonophagocytic activity (56.1%-100% in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 61.1%-100% in the PHiD-CV + DTPa-IPV-Hib group) were comparable for all serotypes in both PHiD-CV groups. Group differences in antibody responses to the DTPa-IPV-Hib antigens remained within the predefined limit for noninferiority. Safety and reactogenicity profiles were comparable across groups.
: PHiD-CV and DTPa-IPV-Hib were immunogenic and well tolerated when coadministered as a 3-dose primary vaccination course.