Comparison of the Safety and Immunogenicity of a Novel Quadrivalent Meningococcal ACWY-Tetanus Toxoid Conjugate Vaccine and a Marketed Quadrivalent Meningococcal ACWY-Diphtheria Toxoid Conjugate Vaccine in Healthy Individuals 10-25 Years of Age (original) (raw)
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BMC Infectious Diseases, 2013
Background: The best strategy to protect individuals against meningococcal disease is to immunize against multiple serogroups. Immunogenicity, antibody persistence, and safety of the EU-licensed meningococcal ACWYtetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in healthy participants aged 11-55 years from the Philippines and Saudi Arabia.
BMC infectious diseases, 2015
Long-term protection against meningococcal disease is associated with persistence of post-vaccination antibodies at protective levels. We evaluated the bactericidal antibody persistence and safety of the quadrivalent meningococcal serogroups A, C, W and Y tetanus-toxoid conjugate vaccine (MenACWY-TT) and the meningococcal polysaccharide serogroups A, C, W, and Y vaccine (MenACWY-PS) up to 5 years post-vaccination. This phase IIb, open, randomized, controlled study conducted in the Philippines and Saudi Arabia consisted of a vaccination phase and a long-term persistence phase. Healthy adolescents and adults aged 11-55 years were randomized (3:1) to receive a single dose of MenACWY-TT (ACWY-TT group) or MenACWY-PS (Men-PS group). Primary and persistence results up to 3 years post-vaccination have been previously reported. Antibody responses against meningococcal serogroups A, C, W, and Y were assessed by a serum bactericidal antibody assay using rabbit complement (rSBA, cut-off titers...
Pediatric Research
Background The immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine, were assessed in healthy 13–25-year olds who received MenACYW-TT or a CRM-conjugate vaccine (MCV4-CRM) 3–6 years earlier. Methods This phase IIIb open-label trial (NCT04084769) evaluated MenACYW-TT-primed participants, randomized to receive MenACYW-TT alone or with a MenB vaccine, and MCV4-CRM-primed participants who received MenACYW-TT alone. Functional antibodies against serogroups A, C, W and Y were measured using human complement serum bactericidal antibody assay (hSBA). The primary endpoint was vaccine seroresponse (post-vaccination titers ≥1:16 if pre-vaccination titers <1:8; or a ≥4-fold increase if pre-vaccination titers ≥1:8) 30 days post booster. Safety was evaluated throughout the study. Results The persistence of the immune response following primary vaccination with MenACYW-TT was demonstra...
Drugs & Aging, 2013
Background The burden of invasive meningococcal disease is substantial in older adults in whom the case fatality rate is high. Travelers to regions with high rates of meningococcal disease, such as Hajj pilgrims, are at increased risk of meningococcal infection, and disease transmission from travelers to their close contacts has been documented. In younger individuals, meningococcal conjugate vaccines offer advantages over polysaccharide vaccines in terms of duration of protection and boostability, and induction of herd immune effects through reductions in nasopharyngeal carriage of meningococci. To date, few data are available evaluating meningococcal conjugate vaccine use in adults [55 years of age. Objective To evaluate the immunogenicity and safety of quadrivalent meningococcal serogroups A, C, W-135 and Y vaccine with all serogroups conjugated to tetanus toxoid (MenACWY-TT, Nimenrix TM , GlaxoSmithKline, Belgium) and a licensed quadrivalent polysaccharide vaccine (MenPS, Mencevax TM GlaxoSmithKline, Belgium) in adults [55 years of age. Methods This was a phase IIIb, open-label, randomized (3:1), controlled study conducted at one study center in Lebanon. A total of 400 healthy adults between 56 and 103 years of age without previous MenPS or tetanus toxoid vaccination within the previous 5 years or meningococcal conjugate vaccination at any time previously were included. They received a single-dose vaccination with Men-ACWY-TT or MenPS with blood sampling before and 1 month after vaccination. The main outcome measures were serum bactericidal activity (rabbit complement source: rSBA) vaccine response (VR) rate [rSBA titer of C1:32 in initially seronegative subjects (rSBA titer \1:8); C4-fold increase in subjects with pre-vaccination rSBA titers between 1:8 and 1:128, and C2-fold increase in subjects with pre-vaccination rSBA titers C1:128]. The percentages of subjects with rSBA titers C1:8 and C1:128 and rSBA geometric mean titers (GMTs) were assessed. Solicited adverse events were recorded for 4 days following vaccination, and all other adverse events, including the incidence of new onset chronic diseases, were recorded for 31 days after vaccination. Results One month after a single dose of MenACWY-TT, the rSBA VR rate in the MenACWY-TT group was 76.6 % for serogroup A, 80.3 % for serogroup C, 77.5 % for serogroup W-135 and 81.9 % for serogroup Y. VR rates in the MenPS group were 91.7, 84.8, 87.1 and 89.1 %, respectively. One month after vaccination, C93.2 % of subjects in the MenACWY-TT group and C93.9 % in the MenPS group had rSBA titers C1:128. In each group, The study is registered at www.clinicaltrials.gov NCT01235975.
The Pediatric infectious disease journal, 2015
We evaluated antibody persistence after one dose of meningococcal serogroups ACWY tetanus toxoid (MenACWY-TT) or diphtheria toxoid (MenACWY-DT) conjugate vaccines and subsequent booster responses to MenACWY-TT. In the initial phase II, open, multicenter study (NCT00454909), 872 participants aged 10-25 years received one MenACWY-TT or MenACWY-DT dose. In this study (NCT00715910), antibody persistence was evaluated at Year 1, 3 and 5 by serum bactericidal activity assays using human complement (hSBA). At Year 5, all participants received a MenACWY-TT booster dose. Immune responses at one month post-booster were compared to a control group including 101 participants aged 15-30 years who received a primary MenACWY-TT dose. Solicited and unsolicited adverse events were recorded for 4 and 31 days, respectively, followed by a 6-month extended safety follow-up. At Year 5, ≥79.5% of MenACWY-TT-primed (N=170) and MenACWY-DT-primed (N=45) participants had hSBA titers ≥1:8 for MenC, MenW and Me...
Human Vaccines & Immunotherapeutics
A previous phase 3, randomized, multicenter study showed the immunogenicity of a primary vaccination of subjects aged 11 to 17 years with the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) or the quadrivalent meningococcal polysaccharide vaccine (MenACWY-PS). This extension study evaluated the safety and immunogenicity of a MenACWY-TT booster 10 years after receiving a primary dose of either MenACWY-TT or MenACWY-PS. The primary immunogenicity endpoint was booster response, evaluated using serum bactericidal antibody assays with rabbit complement (rSBA), 1 month postbooster. Safety endpoints included the percentage of subjects experiencing local and general adverse events (AEs) ≤4 days after MenACWY-TT booster. Of 229 subjects enrolled, 169 and 58 in the MenACWY-TT and MenACWY-PS groups, respectively, completed the booster phase. The 1 month postbooster response for each serogroup ranged from 81.5% to 95.7% for MenACWY-TT and 66.7% to 94.1% for MenACWY-PS. Similar percentages of MenACWY-TT and MenACWY-PS recipients had a booster response to serogroups A, W, and Y, whereas more MenACWY-TT recipients than MenACWY-PS recipients had a booster response to serogroup C. For the MenACWY-TT and MenACWY-PS groups, respectively, the MenACWY-TT booster elicited rSBA titers ≥1:8 in 100% and ≥98.0% of subjects across all serogroups; 100% and ≥96.1% of all subjects had titers ≥1:128. No new safety signals were observed during the booster phase. In conclusion, a MenACWY-TT booster dose after receiving either a primary dose of MenACWY-TT or MenACWY-PS elicited robust immune responses and was well tolerated. Functional antibody responses last up to 10 years after primary MenACWY-TT vaccination.
The Pediatric Infectious Disease Journal, 2011
Methods We did primary and booster phase 3 studies between March 31, 2008, and Aug 16, 2010, in 70 sites in Europe. We used two series of sponsor-supplied, computer-generated randomisation envelopes to allocate healthy 2 month-old infants to receive routine vaccinations (diphtheria-tetanus-acellular pertussis, inactivated poliovirus, hepatitis B plus Haemophilus influenzae type b, and seven-valent pneumococcal vaccine) wat 2, 4, and 6 months of age alone, or concomitantly with 4CMenB or serogroup C conjugate vaccine (MenC) in: 1) an open-label, lot-to-lot immunogenicity and safety substudy of three 4CMenB lots compared with routine vaccines alone (1:1:1:1, block size eight); or 2) an observer-blind, lot-to-lot safety substudy of three 4CMenB lots compared with MenC (1:1:1:3, block size six). At 12 months, 4CMenB-primed children from either substudy were randomised (1:1, block size two) to receive 4CMenB booster, with or without measles-mumps-rubella-varicella (MMRV) vaccine. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroup B test strains, and on randomly selected subsets of serum samples for routine vaccines; laboratory personnel were masked to assignment. The first coprimary outcome was lot-to-lot consistency (hSBA geometric mean ratio of all lots between 0·5 and 2·0), and the second was an immune response (hSBA titre ≥5) for each of the three strains. The primary outcome for the booster study was immune response to booster dose. Immunogenicity data for 4CMenB were for the modified intention-totreat population, including all infants from the open-label substudy who provided serum samples. The safety population included all participants who contributed safety data after at least one dose of study vaccine. These trials are registered with ClinicalTrials.gov, numbers NCT00657709 and NCT00847145.
Japanese Journal of Infectious Diseases
MenACYW-TT is a quadrivalent meningococcal tetanus toxoid-conjugate vaccine designed to prevent invasive meningococcal disease. The primary objective of this study was to demonstrate non-inferiority of the vaccine seroresponse to a single dose of MenACYW-TT compared to a licensed Meningococcal quadrivalent diphtheria-conjugate vaccine, MCV4-DT. This Phase III double-blind, multi-center study was conducted in meningococcal vaccine-naive participants aged 2-55 years in Japan (NCT04368429; JapicCTI-205288). Participants were randomized 1:1 to MenACYW-TT (n=180) or MCV4-DT (n=180). Functional antibodies against meningococcal serogroups A, C, W, and Y were measured using a serum bactericidal antibody assay with human complement (hSBA) at baseline (D0) and 30 days after vaccination (D30). Seroresponse was defined as post-vaccination titers ≥1:16 for participants with baseline titers <1:8; or ≥4-fold increase for participants with baseline titers ≥1:8. Safety data were collected for 30 days. Non-inferiority of the vaccine seroresponse vs MCV4-DT was demonstrated at D30 for each serogroup (A: 85.6% vs. 65.4%; C: 96.6% vs. 62.6%; W: 87.4% vs. 49.2%; Y: 97.7% vs. 63.5%, respectively). MenACYW-TT was well-tolerated, with no safety concerns identified. In conclusion, when administered as a single dose, MenACYW-TT was well tolerated with a noninferior immune response compared to MCV4-DT, providing a potential alternative vaccine for this population.
Human Vaccines & Immunotherapeutics, 2012
Abbreviations: ACWY-TT, investigational tetravalent serogroups A, C, W-135 and Y conjugate vaccine with all serogroups conjugated to the tetanus toxoid carrier protein; (S)AE, (serious) adverse event; ATP cohort, according-to-protocol cohort; CI, confidence interval; GMC, geometric mean concentration; GMT, geometric mean antibody titer; GSK, GlaxoSmithKline Biologicals; IMD, invasive meningococcal disease; MenPS, tetravalent meningococcal polysaccharide vaccine; rSBA, meningococcal bactericidal titers using rabbit complement as exogenous complement source; VR, vaccine response Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase III, open, controlled study. Adults aged 18-55 years were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre-and 1 month post-vaccination. Adverse events (AEs) were assessed 4 days (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 months after vaccination. The number of vaccinated subjects was 1,247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer $ 1:32 in initially seronegative; $ 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, $ 98.0% of subjects had rSBA titers $ 1:128. Grade 3 solicited AEs were reported in # 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults. This study is registered at clinicaltrials.gov NCT00453986
Human Vaccines & Immunotherapeutics, 2012
Incidence of meningococcal diseases is high in children, and effective vaccines are needed for this age group. In this phase II, open, controlled study, 309 children aged 2-10 years from Finland were randomized (3:1) into two parallel groups to receive one dose of meningococcal acWY-tetanus toxoid conjugate vaccine (acWY-TT group; n = 231) or a licensed meningococcal acWY polysaccharide vaccine (Men-ps group; n = 78). serum bactericidal activity using rabbit complement (rsBa) was evaluated up to three years post-vaccination. exploratory comparisons suggested that rsBa vaccine response rates and geometric mean titers (GMTs) for each serogroup at one month post-vaccination and rsBa GMTs for serogroups a, W-135 and Y up to three years post-vaccination were higher in the acWY-TT compared with Menps group, but did not detect any difference between groups in terms of rsBa-Menc GMTs at three years post-vaccination; this is explained by the higher proportion of children from the Men-ps group who were excluded because they were revaccinated with a monovalent meningococcal serogroup c vaccine due to loss of protective antibody levels against this serogroup. although there was a higher incidence of local reactogenicity in the acWY-TT group, general and unsolicited symptoms reporting rates were comparable in both groups. This study showed that MenacWY-TT was immunogenic with a clinically acceptable safety profile in children aged 2-10 years. MenacWY-TT induced higher functional antibody titers for all serogroups, which persisted longer for serogroups a, W-135 and Y, than the MenacWY polysaccharide vaccine. This study has been registered at www.clinicaltrials.gov NcT00427908.