Immune response, antibody persistence, and safety of a single dose of the quadrivalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine in adolescents and adults: results of an open, randomised, controlled study (original) (raw)
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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.
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.
International Journal of Infectious Diseases, 2012
The immunogenicity and safety of the tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in subjects previously vaccinated with a tetravalent meningococcal polysaccharide vaccine and in subjects without previous meningococcal vaccination. Methods: In this phase II, open, controlled study (NCT00661557), healthy subjects aged 4.5-34 years received one dose of MenACWY-TT at month 0. Subjects in the MPS group (n = 192) had received polysaccharide vaccine in a study conducted 30-42 months earlier; age-matched subjects in the noMPS control group (n = 79) had received no meningococcal vaccination within the past 10 years. Serum bactericidal activity using rabbit complement (rSBA) was measured at month 0 and month 1. Results: At month 1, 97.0% of subjects had rSBA titers 1:128. Post-vaccination rSBA geometric mean titers (GMTs) were 3.9-fold higher than pre-vaccination in both treatment groups. Exploratory analyses showed no statistically significant differences between groups in percentages of subjects with rSBA titers 1:8 and 1:128, but significantly lower rSBA GMTs and vaccine response rates for each serogroup in the MPS versus the noMPS group. MenACWY-TT had an acceptable safety profile in both groups. Conclusions: These results suggest that MenACWY-TT could be used in vaccination programs irrespective of the pre-vaccination status with polysaccharide vaccine.
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...
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.
Journal of the Pediatric Infectious Diseases Society, 2014
Universal immunization of adolescents against meningococcal disease with a quadrivalent meningococcal ACWY (MenACWY) conjugate vaccine is recommended in a number of countries. In a randomized, controlled, observer-blinded, multicenter trial, 1016 participants, 10-25 years of age, were randomly allocated 1:1:1 to receive a single dose of 1 of 2 lots of an investigational tetanus toxoid-conjugated MenACWY vaccine (MenACWY-TT) or a marketed diphtheria toxoid-conjugated MenACWY vaccine (MenACWY-DT). The primary outcome was the noninferiority of the vaccine response after MenACWY-TT (lot A) compared with MenACWY-DT for all 4 serogroups. Vaccine response was defined as a postvaccination human serum bactericidal antibody (hSBA) titer against each of the serogroups of at least 1:8 in persons initially seronegative (<1:4) or as a 4-fold increase in titer pre- to postvaccination in persons initially seropositive (≥1:4). Adverse events (AEs) after immunization were measured 4 and 31 days po...
Vaccine, 2010
A dose-range study assessing immunogenicity and safety of one dose of a new candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine administered in the second year of life and in young children a b s t r a c t Meningococcal disease incidence is highest in young children, yet a tetravalent conjugate vaccine is currently not available for this age group. This study evaluated a single dose of four different ACWY-TT conjugate vaccine formulations in 240 toddlers (12-14 months) and 268 children (3-5 years) compared to licensed age-appropriate control vaccines. In toddlers, rSBA-MenC GMTs for the selected formulation were statistically higher than after monovalent-MenC-conjugate vaccine. In children, rSBA-GMTs against each serogroup were statistically higher than after tetravalent polysaccharide vaccine. The safety profile was comparable to licensed controls. The new ACWY-TT conjugate vaccine promises high seroprotection levels against meningococcal disease from 1 year of age.
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.