As the aim of the study focussed on serogroup C responses, the responses to the other serogroups were not assessed. Methods Study design and participants This was a Phase III, multi-center, modified double-blind trial conducted to evaluate the immunogenicity of the serogroup C response and safety of a single dose of the MenACYW-TT vaccine versus a quadrivalent or monovalent C tetanus toxoid conjugate meningococcal vaccine in healthy meningococcal vaccine-na?ve toddlers aged 12C23?months (EudraCT #: 2018C003790C10; “type”:”clinical-trial”,”attrs”:”text”:”NCT03890367″,”term_id”:”NCT03890367″NCT03890367). in toddlers (12C23?months). In this modified, double-blind Phase III study (“type”:”clinical-trial”,”attrs”:”text”:”NCT03890367″,”term_id”:”NCT03890367″NCT03890367), 701 toddlers received one dose of MenACYW-TT (n?=?230), MCV4-TT (n?=?232) or MenC-TT (n?=?239). Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure anti-meningococcal serogroup C antibodies at baseline and 30?days post-vaccination. A sequential statistical approach was used for primary and secondary objectives. For the primary objectives, superiority of serogroup C was assessed in terms of hSBA seroprotection rates (defined as titers 1:8) and GMTs for MenACYW-TT compared Cephapirin Benzathine to MCV4-TT, and rSBA GMTs compared to MenC-TT. The safety of all vaccines within 30?days post-vaccination was described. When administered as a single dose to meningococcal vaccine-na?ve healthy toddlers the superiority of the MenACYW-TT serogroup C immune response versus MCV4-TT was demonstrated for hSBA GMTs (ratio 16.3 [12.7C21.0]) and seroprotection (difference 10.43% [5.68C16.20]); and versus MenC-TT in terms of rSBA GMTs (ratio 1.32 [1.06C1.64]). The safety profiles of a single dose of MenACYW-TT, MCV4-TT and MenC-TT were similar. In meningococcal vaccine-na?ve toddlers, MenACYW-TT induced superior immune responses to serogroup C versus MCV4-TT in terms of hSBA seroprotection and GMTs and versus MenC-TT in terms of rSBA GMTs. strong class=”kwd-title” KEYWORDS: MenACYW-TT, MenC-TT, MCV4-TT, immunogenicity, invasive meningococcal disease, meningococcal serogroup C, seroprotection, superiority, non-inferiority, toddlers Introduction Invasive meningococcal disease (IMD), which typically presents as meningitis and septicemia, had an incidence in Europe of 0.62 cases per 100,000 people in 2018, with the highest incidence in infants and young children; 8.34 cases per 100,000 children 1-year-old and 2.38 cases per 100,000 1C4-year-olds.1,2 The most common causes Cephapirin Benzathine of IMD in Europe are meningococcal serogroups B and C, with an increasing number of cases caused by serogroups W and Y in recent years.3 Brazil has similarly seen the majority of its IMD cases caused by serogroups B, C and W and has reported an incidence of 0.50 cases per 100,000 as of 2018,4 while Australia has seen a significant proportion of its cases caused by serogroups B and W, with cases caused by serogroup C comparatively low following the introduction of a meningococcal serogroup C (MenC) conjugate vaccine immunization program.5 MenC vaccine immunization programs were also launched in the UK and the Netherlands in response to the 1999C2001 serogroup C outbreaks,6 successfully reducing overall disease incidence of IMD caused by serogroup C in both countries.7C9 In response to the recent increases in serogroup W in Europe,10,11 quadrivalent meningococcal conjugate vaccines (MCV4) have been progressively introduced, replacing MenC conjugate vaccines in national immunization programs in several countries.12 Among those countries that recommend meningococcal vaccination during childhood, some use a mixture of MenC and MCV4 vaccines according to the age group, while others still offer exclusively MenC, or exclusively MCV4. MenACYW-TT (MenQuadfi?, Sanofi Pasteur, USA) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed from 12?months of age in Europe and other countries, such as Brazil, Australia and Canada, and licensed for use in individuals from 2?years of age in the US. The development for use in infants from 6?weeks of age is still ongoing.13C21 The immunogenicity and safety of this vaccine has been compared to a licensed MCV4-TT (Nimenrix?, Pfizer, Sandwich, Cephapirin Benzathine UK) in two studies in toddlers aged 12C23?months in Europe.19,20 In the pivotal phase III study, MenACYW-TT demonstrated non-inferiority for seroprotection (defined as titers 1:8) against all four meningococcal serogroups versus MCV4-TT using a human complement serum bactericidal assay (hSBA); for serogroup C, the lower bound of the two-sided 95% CI of the overall Cephapirin Benzathine difference of the proportion seroprotected was greater than 0.20 The tetanus toxoid conjugate monovalent meningococcal C vaccine, MenC-TT (NeisVac-C?, Pfizer, Sandwich, UK), is used extensively worldwide as part of meningococcal C vaccination programs and its immunogenicity was evaluated during vaccine development using the baby rabbit complement serum bactericidal assay (rSBA). To date, the serogroup C response to the MenACYW-TT vaccine has not been directly compared to MenC-TT. The objective of this study was to compare the Rabbit Polyclonal to TACC1 immune response to serogroup C elicited by a single dose of MenACYW-TT to the response elicited by a single dose of MCV4-TT or MenC-TT, and to describe the safety of healthy meningococcal vaccine-na?ve toddlers. Using a sequential testing approach, the serogroup C immunogenicity of MenACYW-TT in terms of seroprotection rates and GMTs was tested for non-inferiority to the immunogenicity of MCV4-TT (measured by hSBA) and MenC-TT (measured by rSBA). If seroprotection rates and GMTs were non-inferior,.
As the aim of the study focussed on serogroup C responses, the responses to the other serogroups were not assessed
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