Effect of Vaccination with Carrier Protein on Response to Meningococcal C Conjugate Vaccines and Value of Different Immunoassays as Predictors of Protection (original) (raw)
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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...
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.
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...
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.
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.
Vaccine, 2012
Background: To assess antibody titers afforded by meningococcal C-(MenC) tetanus toxoid conjugate vaccine at 12 months of age in three different immunization schedules. Methods: This prospective study included three similar cohorts of healthy infants from 1-dose, 2-dose and 3-dose MenC infant immunization programs. Infants were enrolled at 12 months of age and given the final scheduled dose of MenC-tetanus toxoid conjugate vaccine with sera collected prior to and 1 month after the vaccination. Serum bactericidal activity (SBA) titers ≥ 1:8 were considered protective. Results: Before the 12 month dose, participants had significantly different protective titers according to the number of prior doses received: 100% (95% CI 97.6-100%) of infants who had 2 prior doses (at 2 and 4 months) were protected compared to 84.0% (76.7-89.3%) of participants with one dose (at 2 months) and 27.6% (21.0-35.4%) of unvaccinated infants. All subjects were protected after the 12 month MenC dose, but titers were higher with prior priming. Conclusions: Two MenC doses given in infancy afford optimal protection during the first year of life; however, substantial protection was seen after one dose at 2 months.
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.
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...
The Journal of Infectious Diseases, 2002
Healthy adults, 18-55 years old, were immunized once with a tetravalent (serogroups A, C, Y, and W-135) meningococcal vaccine conjugated to diphtheria toxoid at 1 of 3 doses and were monitored for safety, reactogenicity, and immunogenicity. No immediate reactions were observed. Only 1 of 89 subjects reported fever; only 1 reported any severe reactogenicity (local pain/soreness, chills, arthralgia, anorexia, and malaise). For each serogroup and in each dose group, the geometric mean serum bactericidal antibody (SBA) titer and immunoglobulin G concentration increased after immunization. In the 4-and 10-mg-dose groups, all subjects had SBA titers у8 against serogroups A and C, and 89% and 93% of subjects had SBA titers у8 against serogroups Y and W-135, respectively. The A, C, Y, and W-135 Neisseria meningitidis-diphtheria toxoid conjugate vaccine, when given to healthy adults as a single intramuscular injection of 1, 4, or 10 mg/serogroup, is acceptably tolerated and immunogenic and deserves further development. Neisseria meningitidis is a common cause of serious bacterial infection around the world. Infants, immunocompromised individuals, and young adults living in close quarters are at a higher risk for invasive meningococcal disease than the general population [1]. Annually, 2500-3500 cases of meningococcal infection are reported in the United States, for a crude population incidence rate of ∼1 case/100,000 persons/year [2]. The meningococcus has 13 serogroups, distinguished by differences in the composition of repeating polysaccharide units of the capsule. Immunologic response to these antigens is serogroup specific and is important in protection from invasive disease [3, 4]. Infections in the United States occur sporadically or in small clusters, and the most common serogroups involved are B, C, and Y [5]. In some parts of the developing world,