Munc-18

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 4143 Experts worldwide ranked by ideXlab platform

Dominique Boutriau - One of the best experts on this subject based on the ideXlab platform.

  • a combined haemophilus influenzae type b neisseria meningitidis serogroup c tetanus toxoid conjugate vaccine is immunogenic and well tolerated when coadministered with diphtheria tetanus acellular pertussis hepatitis b inactivated poliovirus at 3 5 and 11 months of age results of an open randomized controlled study
    Pediatric Infectious Disease Journal, 2013
    Co-Authors: Timo Vesikari, Narcisa Mesaros, Maria Giuseppina Desole, Giuseppe Ferrera, Aino Forsten, Magalie Caubet, Dominique Boutriau
    Abstract:

    Background This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. Methods In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. Results One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. Conclusions The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.

  • persistence of antibody response following a booster dose of hib menc tt glycoconjugate vaccine to five years a follow up study
    Pediatric Infectious Disease Journal, 2012
    Co-Authors: Ameneh Khatami, Sharon Westcar, Dominique Boutriau, Narcisa Mesaros, Jacek Wysocki, Matthew D Snape, Tessa M John, Kavitha Peddiraju, Andrew J Pollard
    Abstract:

    BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) persist better to 31/2 years of age after a 12-month booster dose of a combination Hib-MenC glycoconjugate vaccine (Hib-MenC-TT) in children primed in infancy with Hib-MenC-TT and diphtheria-tetanus-acellular-pertussis-inactivated poliovirus vaccine (DTaP-IPV) than in those who received a monovalent MenC-CRM197 and DTaP-IPV-Hib (also TT conjugated). Pertussis antibodies against filamentous hemagglutinin and pertactin are higher at 5 and 12 months in children who received DTaP-IPV compared with those immunized with DTaP-IPV-Hib. We evaluated whether these differences persisted to later childhood, following a preschool booster of DTaP-IPV at 31/2 years of age. METHODS: Children in the United Kingdom and Poland previously enrolled in the aforementioned randomized-controlled trial had a blood sample taken at 5 years of age. Antipolyribosylribitol phosphate (Hib) IgG and MenC bactericidal antibody (baby rabbit complement) titers were compared between those immunized in infancy (at 2, 3 and 4 months) with DTaP-IPV/Hib-MenC-TT (Hib-MenC-TT group) and those who received DTaP-IPV-Hib with a monovalent MenC-CRM197 (control group). Antibody concentrations against filamentous hemagglutinin, pertactin and pertussis toxin were also measured at this visit. RESULTS: Two hundred sixty-eight participants aged 58-64 months were enrolled. MenC baby rabbit complement titers ≥1:8 were seen in 115 of 194 of the Hib-MenC-TT group (59.3% [52.0-66.3%]) and 26 of 58 (44.8% [31.7-58.5%]) of control group participants. MenC baby rabbit complement geometric mean titers were 30.4 and 11.3, respectively (ratio 2.70 [1.55-.73]). Antipolyribosylribitol phosphate (Hib) IgG concentrations ≥ 1.0 μg/mL were seen in 171 of 197 (86.8% [81.3-91.2%]) of the Hib-MenC-TT group and 36 of 58 (62.1% [48.4-74.5%]) of control group participants. Antipolyribosylribitol phosphate IgG geometric mean concentrations (GMCs) were 3.82 and 1.67, respectively (ratio 2.29 [1.59-3.28]). Sixty-eight UK participants aged 58-63 months had sera analyzed for the pertussis antigens (44 DTaP-IPV recipients, 14 DTaP-IPV-Hib recipients). Antipertussis toxin IgG GMCs were similar for participants immunized with DTaP-IPV and DTaP-IPV-Hib: 8.2 EL.U/mL (6.1-10.9) compared with 7.2 EL.U/mL (3.9-13.4). Antifilamentous hemagglutinin IgG GMCs were higher for DTaP-IPV recipients (164.7 EL.U/mL [119.4-227.1]) compared with DTaP-IPV-Hib recipients (66.8 EL.U/mL [43.8-101.7]), as were antipertactin IgG GMCs: 102.8 EL.U/mL (67.1-157.3) compared with 23.4 EL.U/mL (15.1-36.2). CONCLUSION: Vaccines used for infant immunization against Hib and MenC differ in their ability to prime responses to a booster dose of Hib-MenC-TT, and this difference persists to at least 5 years of age. Persistence of antipertussis antibody following a preschool booster of DTaP-IPV is also influenced by immunizations received at 2, 3 and 4 months of age, underlining the importance of infant immune priming in the maintenance of antibody levels through childhood. Copyright © 2012 by Lippincott Williams &Wilkins.

  • persistence of immunity following a booster dose of haemophilus influenzae type b meningococcal serogroup c glycoconjugate vaccine follow up of a randomized controlled trial
    Pediatric Infectious Disease Journal, 2011
    Co-Authors: Ameneh Khatami, Tessa John, Sharon Westcar, Chaam Klinger, Llinos Rollinson, Dominique Boutriau, Narcisa Mesaros, Jacek Wysocki, Matthew D Snape, Andrzej Galaj
    Abstract:

    BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) wane after early infant immunization. METHODS: Children previously immunized in a randomized controlled trial at ages 2, 3, and 4 months with DTPa-IPV-Hib and MenC-CRM197 (MenC-CRM group) or DTPa-IPV and Hib-MenC-TT (Hib-MenC-TT group) had blood samples drawn at 1 and 2 years following a booster dose of Hib-MenC-TT at 12 to 15 months of age. A blood sample was also drawn at the year 2 follow-up from a separately recruited age-matched control group who had not received a booster. RESULTS: In 271 children at year 1, mean 14.6 months (range: 12-18 months) following the Hib-MenC-TT booster, MenC bactericidal titers above the protective threshold (rSBA ≥1:8) was demonstrated in 89.0% of the Hib-MenC-TT group and 69.5% of MenC-CRM participants. Antipolyribosylribitol phosphate Ig ≥1.0 μg/mL (Hib correlate for long-term protection) was seen in 94.9% and 82.5%, respectively.In 379 participants (including 72 control children) at year 2 (age: 39-43 months, 25-31 months post Hib-MenC-TT) persistence of MenC antibodies was demonstrated in 67.1% of the Hib-MenC-TT group and 40.5% of the MenC-CRM group, compared with 44.1% of control group participants. Antipolyribosylribitol phosphate Ig ≥1.0 μg/mL was seen in 89.0%, 74.7%, and 38.9%, respectively. CONCLUSIONS: A toddler Hib-MenC-TT booster helps sustain immunity against Hib to 31/2 years of age. Persistence of MenC antibody is similar in children primed with MenC-CRM197 in infancy who receive a booster Hib-MenC-TT, to those who receive no booster. Persistence of MenC antibody is better when primed and boosted with Hib-MenC-TT. © 2011 Lippincott Williams & Wilkins, Inc.

  • immune response and one year antibody persistence after a fourth dose of a novel haemophilus influenzae type b and neisseria meningitidis serogroups c and y tetanus toxoid conjugate vaccine hibmency at 12 to 15 months of age
    Pediatric Infectious Disease Journal, 2010
    Co-Authors: Gary S Marshall, Dominique Boutriau, Jan Poolman, Colin D Marchant, Mark M Blatter, Emmanuel Aris, Leonard R Friedland, Jacqueline M Miller
    Abstract:

    A total of 236 infants received a fourth Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY) dose at 12 to 15 months. One month later, the proportion with anti-PRP antibody > or =1.0 microg/mL and bactericidal titers > or =1:8 to MenC and MenY was 98.9%, 96.9%, and 95.4%, respectively. One year later, anti-PRP concentrations > or =0.15 microg/mL, and MenC and MenY bactericidal titers > or =1:8 persisted in 100%, 96.6%, and 83.8%, respectively. The safety profile of HibMenCY was comparable to Hib.

  • a novel combined hib menc tt glycoconjugate vaccine as a booster dose for toddlers a phase 3 open randomised controlled trial
    Archives of Disease in Childhood, 2008
    Co-Authors: David Pace, Sharon Westcar, Jacek Wysocki, Claire Oluwalana, Lymee Yu, Norman Begg, Hanna Czajka, Gudrun Maechler, Matthew D Snape, Dominique Boutriau
    Abstract:

    Objective: To study the immunogenicity and reactogenicity of a combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT), when administered as a booster dose in combination with a measles, mumps and rubella vaccine (MMR). Design: A phase 3 open randomised controlled trial. Setting: One centre in Oxford, UK and nine centres in Poland Subjects: 12-15 month old healthy children Interventions: In the primary stage of the study 500 healthy, 6-12 week old infants were randomised in a 3:1 ratio to receive Hib-MenC-TT + DTPa-IPV or MenC-CRM197 vaccine + DTPa-IPV-Hib. In the booster stage 476 of participants, 190 in the UK and 286 in Poland, were vaccinated with Hib-MenC-TT and MMR. Main outcome measures: The proportion of children with protective serum antibody levels against MenC and Hib, 6 weeks following a Hib-MenC-TT booster dose. Results: The co-primary objectives were met: the Hib-MenC-TT booster dose induced protective antibody titres in children who were vaccinated with a combination of Hib-MenC-TT + DTPa-IPV or MenC-CRM197 + DTPa-IPV-Hib at 2, 3 and 4 months of age. 94.8% (LL 95%CI 92.4) of participants had rSBA-MenC ≥1:128 and 100% (LL 95%CI 99.2) achieved anti-PRP concentrations ≥1.0μg/ml. The percentage of toddlers with a post boost rSBA-MenC of 1:128 was significantly higher after priming with Hib-MenC-TT (97.7%) than after MenC-CRM197 (86%) (difference: 11.7%; 95%CI 6.2 to 19.4). Conclusion: The waning antibody titres against Hib and MenC following primary immunisation can be boosted to protective levels by administering a dose of the Hib-MenC-TT vaccine at 12-15 months of age, supporting the recent introduction of this vaccine in the UK immunisation schedule to sustain protection of children against Hib and MenC disease. Trial registration: Clinical trials.gov, NCT00258700. Study ID: 103974.

Ameneh Khatami - One of the best experts on this subject based on the ideXlab platform.

  • use of a booster dose of capsular group c meningococcal glycoconjugate vaccine to demonstrate immunologic memory in children primed with one or two vaccine doses in infancy
    Vaccine, 2016
    Co-Authors: David Pace, Ameneh Khatami, Simon Attardmontalto, Merryn Voysey, Paul T Heath, Saul N Faust, Adam Finn, Ray Borrow, Matthew D Snape
    Abstract:

    Background - Use of a polysaccharide vaccine challenge to demonstrate immunologic memory after priming with capsular group C meningococcal conjugate vaccines (MenCC) risks induction of immunologic hyporesponsiveness. For this reason, MenCC vaccines are now used as probes of immunologic memory, however, no studies have demonstrated their ability to distinguish primed from unprimed children. Methods - This study was part of a randomised controlled trial investigating the immunogenicity of a booster dose of the combined Haemophilus influenzae type b and MenC-tetanus toxoid vaccine (Hib-MenC-TT) in infants receiving reduced dose MenCC vaccine priming schedules (one MenC-CRM/MenC-TT or two MenC-CRM vaccine doses) compared with an unprimed group. Antibody kinetics were studied in a subset of 269 children by measuring changes in the MenC serum bactericidal antibody, using rabbit complement, (MenC rSBA) titres and MenC specific IgG memory B-cells before and at 6 and 28 days following the 12 month booster vaccination. Results - At 6 days after the 12 month MenCC vaccine, the rise in MenC rSBA titres and MenC specific IgG memory B-cells of the primed groups were significantly higher than the infant MenCC naive group. Participants primed with one MenC-TT dose had the highest increase in MenC rSBA titres compared with all other groups. The MenC rSBA titres at the 28th compared with the 6th day after boosting was significantly higher in those primed with a single MenC-TT/MenC-CRM vaccine in infancy compared with those who were not primed or who were primed with two doses of the MenC-CRM vaccine. Conclusion - Immunologic memory can be demonstrated by a MenCC booster vaccination but is affected by the type and number of MenCC doses used for infant priming. The MenC rSBA responses can be used to demonstrate successful immunologic priming.

  • immunogenicity of reduced dose priming schedules of serogroup c meningococcal conjugate vaccine followed by booster at 12 months in infants open label randomised controlled trial
    BMJ, 2015
    Co-Authors: David Pace, Ameneh Khatami, Jennifer Mckenna, Danielle Campbell, Simon Attardmontalto, Merryn Voysey, Catherine White, Jacqueline Birks, Adam Finn, Emma Macloed
    Abstract:

    OBJECTIVE: To determine whether the immunogenicity of a single dose infant priming schedule of serogroup C meningococcal (MenC) conjugate vaccine is non-inferior to a two dose priming schedule when followed by a booster dose at age 12 months. DESIGN: Phase IV open label randomised controlled trial carried out from July 2010 until August 2013 SETTING: Four centres in the United Kingdom and one centre in Malta. PARTICIPANTS: Healthy infants aged 6-12 weeks followed up until age 24 months. INTERVENTIONS: In the priming phase of the trial 509 infants were randomised in a 10:10:7:4 ratio into four groups to receive either a single MenC-cross reacting material 197 (CRM) dose at 3 months; two doses of MenC-CRM at 3 and 4 months; a single MenC-polysaccharide-tetanus toxoid (TT) dose at 3 months; or no MenC doses, respectively. Haemophilus influenzae type b (Hib)-MenC-TT vaccine was administered to all infants at 12 months of age. All infants also received the nationally routinely recommended vaccines. Blood samples were taken at age 5, 12, 13, and 24 months. MAIN OUTCOME MEASURE: MenC serum bactericidal antibody assay with rabbit complement (rSBA) one month after the Hib-MenC-TT vaccine. Non-inferiority was met if the lower 95% confidence limit of the difference in the mean log10 MenC rSBA between the single dose MenC-CRM and the two dose MenC-CRM groups was >-0.35. RESULTS: The primary objective was met: after a Hib-MenC-TT booster dose at 12 months of age the MenC rSBA geometric mean titres induced in infants primed with a single MenC-CRM dose were not inferior to those induced in participants primed with two MenC-CRM doses in infancy (660 (95% confidence interval 498 to 876) v 295 (220 to 398)) with a corresponding difference in the mean log10 MenC rSBA of 0.35 (0.17 to 0.53) that showed superiority of the single over the two dose schedule). Exploration of differences between the priming schedules showed that one month after Hib-MenC-TT vaccination, MenC rSBA ≥ 1:8 was observed in >96% of participants previously primed with any of the MenC vaccine schedules in infancy and in 83% of those who were not vaccinated against MenC in infancy. The MenC rSBA geometric mean titres induced by the Hib-MenC-TT boost were significantly higher in children who were primed with one rather than two MenC-CRM doses in infancy. Only priming with MenC-TT, however, induced robust MenC bactericidal antibody after the Hib-MenC-TT booster that persisted until 24 months of age. CONCLUSIONS: MenC vaccination programmes with two MenC infant priming doses could be reduced to a single priming dose without reducing post-boost antibody titres. When followed by a Hib-MenC-TT booster dose, infant priming with a single MenC-TT vaccine dose induces a more robust antibody response than one or two infant doses of MenC-CRM. Bactericidal antibody induced by a single Hib-MenC-TT conjugate vaccine dose at 12 months of age (that is, a toddler only schedule), without infant priming, is not well sustained at 24 months. Because of rapid waning of MenC antibody, programmes using toddler only schedules will still need to rely on herd protection to protect infants and young children.Trial registration Eudract No: 2009-016579-31; NCT01129518; study ID: 2008_06 (http://clinicaltrials.gov).

  • phase ii study of a three dose primary vaccination course of dtpa ipv hib menc tt followed by a 12 month hib menc tt booster in healthy infants
    Pediatric Infectious Disease Journal, 2013
    Co-Authors: Ameneh Khatami, Brigitte Ohenekena, Claudia Oeser, Louise Michaelis, Heather Smee, Matthew D Snape, K. Young, E Macleod, O Van Der Meeren, Maarten Leyssen
    Abstract:

    Aim: To test for immunologic noninferiority of antibody responses to Hib and MenC using a 6-in-1 combination vaccine (DTPa-IPV/Hib-MenCTT) compared with DTPa-IPV-Hib plus MenC-CRM197, before and after a 12-month Hib-MenC-TT booster. Methods: Pragmatic open-label, randomized, multicenter, UK study. "6-in1" group received DTPa-IPV/Hib-MenC-TT at 2, 3 and 4 months; control group received DTPa-IPV-Hib at 2, 3 and 4 months and MenC-CRM197 at 3 and 4 months. Both groups received Hib-MenC-TT at 12 months. Concomitant vaccines: pneumococcal conjugate vaccine at 2, 4 and 13 months, and measles, mumps and rubella vaccine at 13 months. Results: One hundred forty-two children were randomized to each group. One hundred children in the "6-in-1" group and 112 control group children completed the study according-to-protocol. One month postprimary immunizations: 100% of "6-in-1" group and 93.3% of control children had anti- polyribosylribitol phosphate (PRP) IgG ≥0.15 μg/mL; 96.2% and 100%, respectively, had rSBA-MenC titers ≥1:8. One month after booster all children met these thresholds, with anti-PRP geometric mean concentrations of 66.7 (53.3; 83.5) in "6-in-1" recipients and 26.9 (20.9; 34.6) in control children (4.4 [3.5; 5.4] and 3.0 [2.2-4.2] postprimary immunizations, respectively,). rSBA-MenC geometric mean titers were 3062.9 (2421.2; 3874.6) and 954.0 (761.3; 1195.5), respectively, postbooster and 393.2 (292.5; 528.7) and 3110.5 (2612; 3704.2) postprimary. Conclusion: Noninferiority of DTPa-IPV/Hib-MenC-TT compared with DTPa-IPV/Hib plus MenC-CRM197 was demonstrated. In the "6-in-1" group, lower postprimary and greater postbooster rSBA-MenC geometric mean titers suggest memory B-cell priming may be favored by this vaccine over plasma cell induction. Furthermore, greater immunogenicity of TT conjugates used in both primary and booster vaccines in this group may be important. Copyright © 2013 by Lippincott Williams & Wilkins.

  • persistence of antibody response following a booster dose of hib menc tt glycoconjugate vaccine to five years a follow up study
    Pediatric Infectious Disease Journal, 2012
    Co-Authors: Ameneh Khatami, Sharon Westcar, Dominique Boutriau, Narcisa Mesaros, Jacek Wysocki, Matthew D Snape, Tessa M John, Kavitha Peddiraju, Andrew J Pollard
    Abstract:

    BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) persist better to 31/2 years of age after a 12-month booster dose of a combination Hib-MenC glycoconjugate vaccine (Hib-MenC-TT) in children primed in infancy with Hib-MenC-TT and diphtheria-tetanus-acellular-pertussis-inactivated poliovirus vaccine (DTaP-IPV) than in those who received a monovalent MenC-CRM197 and DTaP-IPV-Hib (also TT conjugated). Pertussis antibodies against filamentous hemagglutinin and pertactin are higher at 5 and 12 months in children who received DTaP-IPV compared with those immunized with DTaP-IPV-Hib. We evaluated whether these differences persisted to later childhood, following a preschool booster of DTaP-IPV at 31/2 years of age. METHODS: Children in the United Kingdom and Poland previously enrolled in the aforementioned randomized-controlled trial had a blood sample taken at 5 years of age. Antipolyribosylribitol phosphate (Hib) IgG and MenC bactericidal antibody (baby rabbit complement) titers were compared between those immunized in infancy (at 2, 3 and 4 months) with DTaP-IPV/Hib-MenC-TT (Hib-MenC-TT group) and those who received DTaP-IPV-Hib with a monovalent MenC-CRM197 (control group). Antibody concentrations against filamentous hemagglutinin, pertactin and pertussis toxin were also measured at this visit. RESULTS: Two hundred sixty-eight participants aged 58-64 months were enrolled. MenC baby rabbit complement titers ≥1:8 were seen in 115 of 194 of the Hib-MenC-TT group (59.3% [52.0-66.3%]) and 26 of 58 (44.8% [31.7-58.5%]) of control group participants. MenC baby rabbit complement geometric mean titers were 30.4 and 11.3, respectively (ratio 2.70 [1.55-.73]). Antipolyribosylribitol phosphate (Hib) IgG concentrations ≥ 1.0 μg/mL were seen in 171 of 197 (86.8% [81.3-91.2%]) of the Hib-MenC-TT group and 36 of 58 (62.1% [48.4-74.5%]) of control group participants. Antipolyribosylribitol phosphate IgG geometric mean concentrations (GMCs) were 3.82 and 1.67, respectively (ratio 2.29 [1.59-3.28]). Sixty-eight UK participants aged 58-63 months had sera analyzed for the pertussis antigens (44 DTaP-IPV recipients, 14 DTaP-IPV-Hib recipients). Antipertussis toxin IgG GMCs were similar for participants immunized with DTaP-IPV and DTaP-IPV-Hib: 8.2 EL.U/mL (6.1-10.9) compared with 7.2 EL.U/mL (3.9-13.4). Antifilamentous hemagglutinin IgG GMCs were higher for DTaP-IPV recipients (164.7 EL.U/mL [119.4-227.1]) compared with DTaP-IPV-Hib recipients (66.8 EL.U/mL [43.8-101.7]), as were antipertactin IgG GMCs: 102.8 EL.U/mL (67.1-157.3) compared with 23.4 EL.U/mL (15.1-36.2). CONCLUSION: Vaccines used for infant immunization against Hib and MenC differ in their ability to prime responses to a booster dose of Hib-MenC-TT, and this difference persists to at least 5 years of age. Persistence of antipertussis antibody following a preschool booster of DTaP-IPV is also influenced by immunizations received at 2, 3 and 4 months of age, underlining the importance of infant immune priming in the maintenance of antibody levels through childhood. Copyright © 2012 by Lippincott Williams &Wilkins.

  • phase ii study of a three dose primary vaccination course of dtpa ipv hib menc tt followed by a 12 month hib menc tt booster in healthy infants
    Archives of Disease in Childhood, 2012
    Co-Authors: Ameneh Khatami, Paul T Heath, Brigitte Ohenekena, Claudia Oeser, Louise Michaelis, E Mcleod, Heather Smee, Saul N Faust, K. Young, Adam Finn
    Abstract:

    Aims Combining the licensed Haemophilus influenzae type b (Hib) and serogroup C meningococcal (MenC) conjugate vaccine (Hib-MenC-TT) and DTaP-IPV vaccine could reduce the number of injections needed to administer the United Kingdom routine infant immunisation schedule. We aimed to demonstrate immunologic non-inferiority for Hib and MenC using a 6-in-1 combination vaccine (DTPa-IPV/Hib-MenC-TT) compared to a schedule using DTPa-IPV-Hib-TT and MenC-CRM197 conjugate vaccines. Secondary objectives included demonstration of non-inferiority of diphtheria, tetanus and polio immunogenicity; persistence of immune response to all antigens at 12 months of age and the response to a 12 month Hib-MenC-TT booster. Methods Open-label, randomised, multi-centre, UK study. Combination group received DTPa-IPV/Hib-MenC-TT at 2, 3, 4 months. Control group received DTPa-IPV-Hib-TT at 2, 3, 4 months and MenC-CRM197 at 3, 4 months. Both groups received Hib-MenC-TT booster at 12 months. Concomitant vaccines: pneumococcal conjugate vaccine at 2, 4, 13 months; MMR at 13 months. Blood tests were performed at 4, 5, 12 and 13 months. Results 142 children were randomised in each group. 100 children were included in the according-to-protocol cohort for analysis of immunogenicity following the booster vaccine in the combination group; and 112 children in the control group. One month post-primary immunisations 100% of the combination group and 93.3 % of control children had anti-PRP IgG concentration ≥0.15 μg/mL. 96.2% and 100% respectively had rSBA-MenC titres ≥1:8. One month post-booster all children met these thresholds. At 13 months of age, anti-PRP geometric mean concentrations (with 95% confidence intervals) were 66.7 (53.3-83.5) in the combination group and 26.9 (20.9-34.6) in the control group (4.35 [3.51-5.39] and 3.04 [2.21-4.19] respectively at 5 months). rSBA-MenC geometric mean titres (GMTs) were 3062.9 (2421.2-3874.6) and 954.0 (761.3-1195.5) respectively (393.2 [292.5-528.7] and 3110.5 [2612-3704.2] respectively at 5 months). Conclusion Non-inferiority of DTPa-IPV/Hib-MenC-TT compared to DTPa-IPV-Hib-TT plus MenC-CRM197 was demonstrated. The lower rSBA-MenC GMTs after primary immunisations and greater booster responses in the combination group suggest that immune priming might be inversely related to post-primary antibody responses. Furthermore, greater immunogenicity of TT conjugates used in primary and booster MenC vaccines in this group may be important.

Matthew D Snape - One of the best experts on this subject based on the ideXlab platform.

  • use of a booster dose of capsular group c meningococcal glycoconjugate vaccine to demonstrate immunologic memory in children primed with one or two vaccine doses in infancy
    Vaccine, 2016
    Co-Authors: David Pace, Ameneh Khatami, Simon Attardmontalto, Merryn Voysey, Paul T Heath, Saul N Faust, Adam Finn, Ray Borrow, Matthew D Snape
    Abstract:

    Background - Use of a polysaccharide vaccine challenge to demonstrate immunologic memory after priming with capsular group C meningococcal conjugate vaccines (MenCC) risks induction of immunologic hyporesponsiveness. For this reason, MenCC vaccines are now used as probes of immunologic memory, however, no studies have demonstrated their ability to distinguish primed from unprimed children. Methods - This study was part of a randomised controlled trial investigating the immunogenicity of a booster dose of the combined Haemophilus influenzae type b and MenC-tetanus toxoid vaccine (Hib-MenC-TT) in infants receiving reduced dose MenCC vaccine priming schedules (one MenC-CRM/MenC-TT or two MenC-CRM vaccine doses) compared with an unprimed group. Antibody kinetics were studied in a subset of 269 children by measuring changes in the MenC serum bactericidal antibody, using rabbit complement, (MenC rSBA) titres and MenC specific IgG memory B-cells before and at 6 and 28 days following the 12 month booster vaccination. Results - At 6 days after the 12 month MenCC vaccine, the rise in MenC rSBA titres and MenC specific IgG memory B-cells of the primed groups were significantly higher than the infant MenCC naive group. Participants primed with one MenC-TT dose had the highest increase in MenC rSBA titres compared with all other groups. The MenC rSBA titres at the 28th compared with the 6th day after boosting was significantly higher in those primed with a single MenC-TT/MenC-CRM vaccine in infancy compared with those who were not primed or who were primed with two doses of the MenC-CRM vaccine. Conclusion - Immunologic memory can be demonstrated by a MenCC booster vaccination but is affected by the type and number of MenCC doses used for infant priming. The MenC rSBA responses can be used to demonstrate successful immunologic priming.

  • phase ii study of a three dose primary vaccination course of dtpa ipv hib menc tt followed by a 12 month hib menc tt booster in healthy infants
    Pediatric Infectious Disease Journal, 2013
    Co-Authors: Ameneh Khatami, Brigitte Ohenekena, Claudia Oeser, Louise Michaelis, Heather Smee, Matthew D Snape, K. Young, E Macleod, O Van Der Meeren, Maarten Leyssen
    Abstract:

    Aim: To test for immunologic noninferiority of antibody responses to Hib and MenC using a 6-in-1 combination vaccine (DTPa-IPV/Hib-MenCTT) compared with DTPa-IPV-Hib plus MenC-CRM197, before and after a 12-month Hib-MenC-TT booster. Methods: Pragmatic open-label, randomized, multicenter, UK study. "6-in1" group received DTPa-IPV/Hib-MenC-TT at 2, 3 and 4 months; control group received DTPa-IPV-Hib at 2, 3 and 4 months and MenC-CRM197 at 3 and 4 months. Both groups received Hib-MenC-TT at 12 months. Concomitant vaccines: pneumococcal conjugate vaccine at 2, 4 and 13 months, and measles, mumps and rubella vaccine at 13 months. Results: One hundred forty-two children were randomized to each group. One hundred children in the "6-in-1" group and 112 control group children completed the study according-to-protocol. One month postprimary immunizations: 100% of "6-in-1" group and 93.3% of control children had anti- polyribosylribitol phosphate (PRP) IgG ≥0.15 μg/mL; 96.2% and 100%, respectively, had rSBA-MenC titers ≥1:8. One month after booster all children met these thresholds, with anti-PRP geometric mean concentrations of 66.7 (53.3; 83.5) in "6-in-1" recipients and 26.9 (20.9; 34.6) in control children (4.4 [3.5; 5.4] and 3.0 [2.2-4.2] postprimary immunizations, respectively,). rSBA-MenC geometric mean titers were 3062.9 (2421.2; 3874.6) and 954.0 (761.3; 1195.5), respectively, postbooster and 393.2 (292.5; 528.7) and 3110.5 (2612; 3704.2) postprimary. Conclusion: Noninferiority of DTPa-IPV/Hib-MenC-TT compared with DTPa-IPV/Hib plus MenC-CRM197 was demonstrated. In the "6-in-1" group, lower postprimary and greater postbooster rSBA-MenC geometric mean titers suggest memory B-cell priming may be favored by this vaccine over plasma cell induction. Furthermore, greater immunogenicity of TT conjugates used in both primary and booster vaccines in this group may be important. Copyright © 2013 by Lippincott Williams & Wilkins.

  • persistence of antibody response following a booster dose of hib menc tt glycoconjugate vaccine to five years a follow up study
    Pediatric Infectious Disease Journal, 2012
    Co-Authors: Ameneh Khatami, Sharon Westcar, Dominique Boutriau, Narcisa Mesaros, Jacek Wysocki, Matthew D Snape, Tessa M John, Kavitha Peddiraju, Andrew J Pollard
    Abstract:

    BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) persist better to 31/2 years of age after a 12-month booster dose of a combination Hib-MenC glycoconjugate vaccine (Hib-MenC-TT) in children primed in infancy with Hib-MenC-TT and diphtheria-tetanus-acellular-pertussis-inactivated poliovirus vaccine (DTaP-IPV) than in those who received a monovalent MenC-CRM197 and DTaP-IPV-Hib (also TT conjugated). Pertussis antibodies against filamentous hemagglutinin and pertactin are higher at 5 and 12 months in children who received DTaP-IPV compared with those immunized with DTaP-IPV-Hib. We evaluated whether these differences persisted to later childhood, following a preschool booster of DTaP-IPV at 31/2 years of age. METHODS: Children in the United Kingdom and Poland previously enrolled in the aforementioned randomized-controlled trial had a blood sample taken at 5 years of age. Antipolyribosylribitol phosphate (Hib) IgG and MenC bactericidal antibody (baby rabbit complement) titers were compared between those immunized in infancy (at 2, 3 and 4 months) with DTaP-IPV/Hib-MenC-TT (Hib-MenC-TT group) and those who received DTaP-IPV-Hib with a monovalent MenC-CRM197 (control group). Antibody concentrations against filamentous hemagglutinin, pertactin and pertussis toxin were also measured at this visit. RESULTS: Two hundred sixty-eight participants aged 58-64 months were enrolled. MenC baby rabbit complement titers ≥1:8 were seen in 115 of 194 of the Hib-MenC-TT group (59.3% [52.0-66.3%]) and 26 of 58 (44.8% [31.7-58.5%]) of control group participants. MenC baby rabbit complement geometric mean titers were 30.4 and 11.3, respectively (ratio 2.70 [1.55-.73]). Antipolyribosylribitol phosphate (Hib) IgG concentrations ≥ 1.0 μg/mL were seen in 171 of 197 (86.8% [81.3-91.2%]) of the Hib-MenC-TT group and 36 of 58 (62.1% [48.4-74.5%]) of control group participants. Antipolyribosylribitol phosphate IgG geometric mean concentrations (GMCs) were 3.82 and 1.67, respectively (ratio 2.29 [1.59-3.28]). Sixty-eight UK participants aged 58-63 months had sera analyzed for the pertussis antigens (44 DTaP-IPV recipients, 14 DTaP-IPV-Hib recipients). Antipertussis toxin IgG GMCs were similar for participants immunized with DTaP-IPV and DTaP-IPV-Hib: 8.2 EL.U/mL (6.1-10.9) compared with 7.2 EL.U/mL (3.9-13.4). Antifilamentous hemagglutinin IgG GMCs were higher for DTaP-IPV recipients (164.7 EL.U/mL [119.4-227.1]) compared with DTaP-IPV-Hib recipients (66.8 EL.U/mL [43.8-101.7]), as were antipertactin IgG GMCs: 102.8 EL.U/mL (67.1-157.3) compared with 23.4 EL.U/mL (15.1-36.2). CONCLUSION: Vaccines used for infant immunization against Hib and MenC differ in their ability to prime responses to a booster dose of Hib-MenC-TT, and this difference persists to at least 5 years of age. Persistence of antipertussis antibody following a preschool booster of DTaP-IPV is also influenced by immunizations received at 2, 3 and 4 months of age, underlining the importance of infant immune priming in the maintenance of antibody levels through childhood. Copyright © 2012 by Lippincott Williams &Wilkins.

  • persistence of serum bactericidal antibody one year after a booster dose of either a glycoconjugate or a plain polysaccharide vaccine against serogroup c neisseria meningitidis given to adolescents previously immunized with a glycoconjugate vaccine
    Pediatric Infectious Disease Journal, 2011
    Co-Authors: Matthew D Snape, Tessa John, Lymee Yu, Dominic F Kelly, Christina Banner, Linda Diggle, Omar Omar, Astrid Borkowski, S Lewis, Andrew J Pollard
    Abstract:

    Background: Bactericidal antibody induced by immunization of infants with serogroup C Neisseria meningitidis (MenC) vaccines wanes rapidly during childhood. Adolescents are at particular risk from meningococcal disease, therefore they might benefit from a booster dose of vaccine. The duration of serologic response to such a booster in adolescents is unknown. Methods: In a previous study, English schoolchildren, aged 9 to 12 years, who had received a monovalent MenC glycoconjugate vaccine in 1999-2000, were given either a plain polysaccharide vaccine (MenC-PS group, n = 150) or a glycoconjugate vaccine (MenC-CRM group, n = 95) at 13 to 15 years of age. In this follow-up study, serum bactericidal antibody titers and specific immunoglobulin G concentrations were assessed 1 year later. Results were compared with unboosted controls of similar age (control group, n = 298). Results: Compliance with study protocol was achieved for 146 of the MenC-PS group, 92 of the MenC-CRM group, and 293 of the control group. Compared with the control group, both the MenC-PS and MenC-CRM groups had a significantly higher (P < 0.0001) geometric mean serum bactericidal antibody titers 1 year after the booster dose (geometric mean titers for MenC-PS group 3388 [95% confidence interval {CI}: 2460-4665]; MenC-CRM group 4417 [95% CI: 2951-6609]; control group 316 [95% CI: 252-396]). Specific immunoglobulin G concentration also rose and remained elevated 1 year after the booster. Conclusions: A booster dose of MenC vaccine given to adolescents produced a marked rise in bactericidal antibody, which remained elevated 1 year later. Introduction of an adolescent booster of MenC vaccine might provide enhanced long-term population control of the disease. © 2011 by Lippincott Williams & Wilkins.

  • persistence of immunity following a booster dose of haemophilus influenzae type b meningococcal serogroup c glycoconjugate vaccine follow up of a randomized controlled trial
    Pediatric Infectious Disease Journal, 2011
    Co-Authors: Ameneh Khatami, Tessa John, Sharon Westcar, Chaam Klinger, Llinos Rollinson, Dominique Boutriau, Narcisa Mesaros, Jacek Wysocki, Matthew D Snape, Andrzej Galaj
    Abstract:

    BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) wane after early infant immunization. METHODS: Children previously immunized in a randomized controlled trial at ages 2, 3, and 4 months with DTPa-IPV-Hib and MenC-CRM197 (MenC-CRM group) or DTPa-IPV and Hib-MenC-TT (Hib-MenC-TT group) had blood samples drawn at 1 and 2 years following a booster dose of Hib-MenC-TT at 12 to 15 months of age. A blood sample was also drawn at the year 2 follow-up from a separately recruited age-matched control group who had not received a booster. RESULTS: In 271 children at year 1, mean 14.6 months (range: 12-18 months) following the Hib-MenC-TT booster, MenC bactericidal titers above the protective threshold (rSBA ≥1:8) was demonstrated in 89.0% of the Hib-MenC-TT group and 69.5% of MenC-CRM participants. Antipolyribosylribitol phosphate Ig ≥1.0 μg/mL (Hib correlate for long-term protection) was seen in 94.9% and 82.5%, respectively.In 379 participants (including 72 control children) at year 2 (age: 39-43 months, 25-31 months post Hib-MenC-TT) persistence of MenC antibodies was demonstrated in 67.1% of the Hib-MenC-TT group and 40.5% of the MenC-CRM group, compared with 44.1% of control group participants. Antipolyribosylribitol phosphate Ig ≥1.0 μg/mL was seen in 89.0%, 74.7%, and 38.9%, respectively. CONCLUSIONS: A toddler Hib-MenC-TT booster helps sustain immunity against Hib to 31/2 years of age. Persistence of MenC antibody is similar in children primed with MenC-CRM197 in infancy who receive a booster Hib-MenC-TT, to those who receive no booster. Persistence of MenC antibody is better when primed and boosted with Hib-MenC-TT. © 2011 Lippincott Williams & Wilkins, Inc.

Andrew J Pollard - One of the best experts on this subject based on the ideXlab platform.

  • persistence of antibody response following a booster dose of hib menc tt glycoconjugate vaccine to five years a follow up study
    Pediatric Infectious Disease Journal, 2012
    Co-Authors: Ameneh Khatami, Sharon Westcar, Dominique Boutriau, Narcisa Mesaros, Jacek Wysocki, Matthew D Snape, Tessa M John, Kavitha Peddiraju, Andrew J Pollard
    Abstract:

    BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) persist better to 31/2 years of age after a 12-month booster dose of a combination Hib-MenC glycoconjugate vaccine (Hib-MenC-TT) in children primed in infancy with Hib-MenC-TT and diphtheria-tetanus-acellular-pertussis-inactivated poliovirus vaccine (DTaP-IPV) than in those who received a monovalent MenC-CRM197 and DTaP-IPV-Hib (also TT conjugated). Pertussis antibodies against filamentous hemagglutinin and pertactin are higher at 5 and 12 months in children who received DTaP-IPV compared with those immunized with DTaP-IPV-Hib. We evaluated whether these differences persisted to later childhood, following a preschool booster of DTaP-IPV at 31/2 years of age. METHODS: Children in the United Kingdom and Poland previously enrolled in the aforementioned randomized-controlled trial had a blood sample taken at 5 years of age. Antipolyribosylribitol phosphate (Hib) IgG and MenC bactericidal antibody (baby rabbit complement) titers were compared between those immunized in infancy (at 2, 3 and 4 months) with DTaP-IPV/Hib-MenC-TT (Hib-MenC-TT group) and those who received DTaP-IPV-Hib with a monovalent MenC-CRM197 (control group). Antibody concentrations against filamentous hemagglutinin, pertactin and pertussis toxin were also measured at this visit. RESULTS: Two hundred sixty-eight participants aged 58-64 months were enrolled. MenC baby rabbit complement titers ≥1:8 were seen in 115 of 194 of the Hib-MenC-TT group (59.3% [52.0-66.3%]) and 26 of 58 (44.8% [31.7-58.5%]) of control group participants. MenC baby rabbit complement geometric mean titers were 30.4 and 11.3, respectively (ratio 2.70 [1.55-.73]). Antipolyribosylribitol phosphate (Hib) IgG concentrations ≥ 1.0 μg/mL were seen in 171 of 197 (86.8% [81.3-91.2%]) of the Hib-MenC-TT group and 36 of 58 (62.1% [48.4-74.5%]) of control group participants. Antipolyribosylribitol phosphate IgG geometric mean concentrations (GMCs) were 3.82 and 1.67, respectively (ratio 2.29 [1.59-3.28]). Sixty-eight UK participants aged 58-63 months had sera analyzed for the pertussis antigens (44 DTaP-IPV recipients, 14 DTaP-IPV-Hib recipients). Antipertussis toxin IgG GMCs were similar for participants immunized with DTaP-IPV and DTaP-IPV-Hib: 8.2 EL.U/mL (6.1-10.9) compared with 7.2 EL.U/mL (3.9-13.4). Antifilamentous hemagglutinin IgG GMCs were higher for DTaP-IPV recipients (164.7 EL.U/mL [119.4-227.1]) compared with DTaP-IPV-Hib recipients (66.8 EL.U/mL [43.8-101.7]), as were antipertactin IgG GMCs: 102.8 EL.U/mL (67.1-157.3) compared with 23.4 EL.U/mL (15.1-36.2). CONCLUSION: Vaccines used for infant immunization against Hib and MenC differ in their ability to prime responses to a booster dose of Hib-MenC-TT, and this difference persists to at least 5 years of age. Persistence of antipertussis antibody following a preschool booster of DTaP-IPV is also influenced by immunizations received at 2, 3 and 4 months of age, underlining the importance of infant immune priming in the maintenance of antibody levels through childhood. Copyright © 2012 by Lippincott Williams &Wilkins.

  • persistence of serum bactericidal antibody one year after a booster dose of either a glycoconjugate or a plain polysaccharide vaccine against serogroup c neisseria meningitidis given to adolescents previously immunized with a glycoconjugate vaccine
    Pediatric Infectious Disease Journal, 2011
    Co-Authors: Matthew D Snape, Tessa John, Lymee Yu, Dominic F Kelly, Christina Banner, Linda Diggle, Omar Omar, Astrid Borkowski, S Lewis, Andrew J Pollard
    Abstract:

    Background: Bactericidal antibody induced by immunization of infants with serogroup C Neisseria meningitidis (MenC) vaccines wanes rapidly during childhood. Adolescents are at particular risk from meningococcal disease, therefore they might benefit from a booster dose of vaccine. The duration of serologic response to such a booster in adolescents is unknown. Methods: In a previous study, English schoolchildren, aged 9 to 12 years, who had received a monovalent MenC glycoconjugate vaccine in 1999-2000, were given either a plain polysaccharide vaccine (MenC-PS group, n = 150) or a glycoconjugate vaccine (MenC-CRM group, n = 95) at 13 to 15 years of age. In this follow-up study, serum bactericidal antibody titers and specific immunoglobulin G concentrations were assessed 1 year later. Results were compared with unboosted controls of similar age (control group, n = 298). Results: Compliance with study protocol was achieved for 146 of the MenC-PS group, 92 of the MenC-CRM group, and 293 of the control group. Compared with the control group, both the MenC-PS and MenC-CRM groups had a significantly higher (P < 0.0001) geometric mean serum bactericidal antibody titers 1 year after the booster dose (geometric mean titers for MenC-PS group 3388 [95% confidence interval {CI}: 2460-4665]; MenC-CRM group 4417 [95% CI: 2951-6609]; control group 316 [95% CI: 252-396]). Specific immunoglobulin G concentration also rose and remained elevated 1 year after the booster. Conclusions: A booster dose of MenC vaccine given to adolescents produced a marked rise in bactericidal antibody, which remained elevated 1 year later. Introduction of an adolescent booster of MenC vaccine might provide enhanced long-term population control of the disease. © 2011 by Lippincott Williams & Wilkins.

  • antibody persistence after serogroup c meningococcal conjugate immunization of united kingdom primary school children in 1999 2000 and response to a booster a phase 4 clinical trial
    Clinical Infectious Diseases, 2010
    Co-Authors: Kirsten P Perrett, A P Winter, Elizabeth Kibwana, Tessa John, Lymee Yu, Ray Borrow, Nigel Curtis, Andrew J Pollard
    Abstract:

    Background. After immunization with serogroup C meningococcal (MenC) conjugate vaccine, antibody responses and vaccine effectiveness are sustained in adolescents, in contrast to rapid waning in young children. We investigated the persistence of serum bactericidal antibody (SBA) titers in children 6 years after immunization with MenC vaccine (primed between 2 months and 6 years of age). The response to a Haemophilus influenzae type b-MenC conjugate (Hib-MenC) booster was also measured. Methods. A phase 4 clinical trial was conducted among 250 healthy 6-12-year-old children. SBA titers were measured before, 1 month after, and 1 year after Hib-MenC administration. The correlate of protection was an SBA titer of ≥8. Results. An SBA titer of ≥8 was observed in 61 (25% [95% confidence interval {CI}, 20%-30%]) of 244 participants (mean age, 9.1 years; mean interval since MenC immunization, 6.75 years). The proportion with an SBA titer of ≥8 and the SBA geometric mean titer increased with age, from 12% (95% CI, 4%-23%) to 48% (95% CI, 29%-67%) and from 2.90 (95% CI, 2.11-3.99) to 17.20 (95% CI, 6.80-43.5), respectively, from a mean age of 7.0 to 12.1 years. One month after the Hib-MenC booster, all participants had an SBA titer of ≥8, which was sustained in 99.6% at 1 year. Conclusions. As a result of waning antibody, the majority of 6-12-year-old children in the United Kingdom have inadequate serological protection against MenC. The persistence of MenC immunity and the response to a Hib-MenC booster is dependent on age at priming. A booster was highly effective in this cohort and could sustain population immunity against MenC disease. Trial registration. Current Controlled Trials (http://www.controlled-trials.com) identifier: ISRCTN72858898. © 2010 by the Infectious Diseases Society of America. All rights reserved.

Jacqueline M Miller - One of the best experts on this subject based on the ideXlab platform.

  • five year antibody persistence and safety after a single dose of combined haemophilus influenzae type b neisseria meningitidis serogroup c tetanus toxoid conjugate vaccine in haemophilus influenzae type b primed toddlers
    Pediatric Infectious Disease Journal, 2015
    Co-Authors: Robert Booy, Terry Nolan, Tanya Stoney, M Van Dier Wielen, D Kohle, Graham Reynolds, Peter Richmond, Helen Marshall, Michael D. Nissen, Jacqueline M Miller
    Abstract:

    Antibody persistence is evaluated in healthy Australian children 4 and 5 years postvaccination with a single dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) compared with separately administered Hib-TT and MenC-CRM197 vaccines (Hib + MCC).This is another follow-up of a phase III, open, randomized, controlled study (NCT00326118), in which 433 Hib-primed but MenC naive toddlers aged 12-18 months were randomized 3:1 to receive Hib-MenC-TT or Hib + MCC vaccines. Protection against (1) MenC was measured by serum bactericidal antibody assay using rabbit complement (rSBA) and (2) Hib was measured by enzyme-linked immunosorbent assay of antibodies to polyribosylribitol phosphate (anti-PRP). Study children were assessed for any potentially vaccine-related serious adverse events at each persistence study visit.The according-to-protocol cohorts for persistence at years 4 and 5 included 282 and 263 children, respectively. The percentages of children with rSBA-MenC titers ≥1:8 at years 4 and 5 were 12.5% and 19.0%, respectively, in the Hib-MenC group; and 12.3% and 25.0% in the Hib + MCC group. All children in each group had anti-PRP concentrations ≥0.15 μg/mL at year 5. Exploratory analyses suggested no potential differences between groups in rSBA-MenC or anti-PRP antibody persistence. No vaccine-related serious adverse events were reported.Antibody persistence was similar for years 4 and 5 after Hib-MenC-TT or Hib + MCC vaccination, with the majority of children retaining anti-PRP antibody concentrations ≥0.15 μg/mL at both timepoints. The percentage of children retaining rSBA-MenC titers ≥1:8 was low (≤25%), suggesting that a MenC booster dose may be warranted before adolescence.

  • a randomized study to evaluate the immunogenicity and safety of a heptavalent diphtheria tetanus pertussis hepatitis b poliomyelitis haemophilus influenzae b and meningococcal serogroup c combination vaccine administered to infants at 2 4 and 12 months of age
    Pediatric Infectious Disease Journal, 2014
    Co-Authors: Franck Thollot, Maarten Leyssen, Heidemarie Pankowculot, David W Scheifele, Brigitte Cheuvart, Liliana Ulianov, Jacqueline M Miller
    Abstract:

    BACKGROUND The immunogenicity and safety of the investigational diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) heptavalent combination vaccine were compared with those of licensed control vaccines. METHODS In this open, phase II, randomized study (NCT01090453), 480 infants from Germany, France and Canada received the heptavalent vaccine (Hepta group) or hexavalent and monovalent MenC control vaccines (HexaMenC group) co-administered with a 13-valent pneumococcal conjugate vaccine at 2, 4 and 12 months of age. Immunogenicity was measured 1 month after the second primary dose, and before and 1 month after the booster dose. Safety and reactogenicity were also evaluated. RESULTS Non-inferiority of immune responses to MenC and Hib induced by 2-dose primary vaccination with the heptavalent vaccine versus control vaccines was demonstrated. In exploratory analyses, postprimary and postbooster functional antibody geometric mean titers against MenC tended to be lower (1119.5 vs. 3200.5; 2653.8 vs. 6028.4) and antibody geometric mean concentrations against Hib higher (1.594 vs. 0.671 μg/mL; 17.678 vs. 13.737 μg/mL) in the Hepta versus the HexaMenC group. The heptavalent and control vaccines were immunogenic to all other antigens, although immune responses to poliovirus were lower than expected in both groups. No differences in safety and reactogenicity profiles were detected between groups. CONCLUSIONS The heptavalent vaccine induced non-inferior MenC and Hib responses compared with control vaccines. Both vaccination regimens, when administered at 2, 4 and 12 months of age, had comparable safety profiles and were immunogenic to all antigens, with lower-than-expected responses to poliomyelitis.

  • immune response and one year antibody persistence after a fourth dose of a novel haemophilus influenzae type b and neisseria meningitidis serogroups c and y tetanus toxoid conjugate vaccine hibmency at 12 to 15 months of age
    Pediatric Infectious Disease Journal, 2010
    Co-Authors: Gary S Marshall, Dominique Boutriau, Jan Poolman, Colin D Marchant, Mark M Blatter, Emmanuel Aris, Leonard R Friedland, Jacqueline M Miller
    Abstract:

    A total of 236 infants received a fourth Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY) dose at 12 to 15 months. One month later, the proportion with anti-PRP antibody > or =1.0 microg/mL and bactericidal titers > or =1:8 to MenC and MenY was 98.9%, 96.9%, and 95.4%, respectively. One year later, anti-PRP concentrations > or =0.15 microg/mL, and MenC and MenY bactericidal titers > or =1:8 persisted in 100%, 96.6%, and 83.8%, respectively. The safety profile of HibMenCY was comparable to Hib.

Related terms

Munc-18 - 15 days free trial to Access Experts & Abstracts