Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) vs. a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine in meningococcal vaccine-naïve and meningococcal C conjugate vaccine-primed toddlers: a phase III randomised study.

Vaccination remains the best strategy to reduce invasive meningococcal disease. This study evaluated an investigational tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT) vs. a licensed tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MCV4-TT) (NCT02955797). Healthy toddlers aged 12-23 months were included if they were either meningococcal vaccine-naïve or MenC conjugate (MCC) vaccine-primed (≥1 dose of MCC prior to 12 months of age). Vaccine-naïve participants were randomised 1:1 to either MenACYW-TT (n = 306) or MCV4-TT (n = 306). MCC-primed participants were randomised 2:1 to MenACYW-TT (n = 203) or MCV4-TT (n = 103). Antibody titres against each of the four meningococcal serogroups were measured by serum bactericidal antibody assay using the human complement. The co-primary objectives of this study were to demonstrate the non-inferiority of MenACYW-TT to MCV4-TT in terms of seroprotection (titres ≥1:8) at Day 30 in both vaccine-naïve and all participants (vaccine-naïve and MCC-primed groups pooled). The immune response for all four serogroups to MenACYW-TT was non-inferior to MCV4-TT in vaccine-naïve participants (seroprotection: range 83.6-99.3% and 81.4-91.6%, respectively) and all participants (seroprotection: range 83.6-99.3% and 81.4-98.0%, respectively). The safety profiles of both vaccines were comparable. MenACYW-TT was well-tolerated and demonstrated non-inferior immunogenicity when administered to MCC vaccine-primed and vaccine-naïve toddlers.

Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix in Healthy Adolescents: A Randomized Phase IIIb Multicenter Study.

INTRODUCTION: Many immunization programs in Europe recommend quadrivalent meningococcal vaccinations, which are often administered concomitantly with other vaccines. We compared the immune response of a tetanus toxoid conjugated quadrivalent meningococcal vaccine (MenACYW-TT, MenQuadfi®) with another quadrivalent meningococcal conjugate vaccine (MCV4-TT; Nimenrix®) when administered alone or concomitantly with Tdap-IPV and 9vHPV vaccines in adolescents. METHODS: In this phase IIIb trial, healthy adolescents (MenC-naïve or MenC-primed before 2 years of age) from Spain, Italy, Hungary, and Singapore were randomized in a 3:3:2 ratio to receive either MenACYW-TT or MCV4-TT alone, or MenACYW-TT concomitantly with 9vHPV and Tdap-IPV. The primary objective was to demonstrate the non-inferiority of the seroprotection rate (human serum bactericidal assay [hSBA] titer ≥ 1:8) to serogroups A, C, W, and Y 30 days post-vaccination with a single dose of MenACYW-TT or MCV4-TT. Secondary objectives included describing hSBA titers for the four serogroups before and 1 month following vaccination and according to MenC priming status. RESULTS: A total of 463 participants were enrolled (MenACYW-TT, n = 173; MCV4-TT, n = 173; MenACYW-TT/9vHPV/Tdap-IPV n = 117). Non-inferiority based on seroprotection was demonstrated for MenACYW-TT versus MCV4-TT for all serogroups. Immune responses were comparable whether MenACYW-TT was administered alone or concomitantly with Tdap-IPV and 9vHPV. Post-vaccination hSBA GMTs were higher in MenACYW-TT vs. MCV4-TT for serogroups C, Y, and W and comparable for serogroup A. The percentages of participants with an hSBA vaccine seroresponse were higher in MenACYW-TT vs. MCV4-TT for all serogroups. For serogroup C, higher GMTs were observed in both MenC-naïve or -primed participants vaccinated with MenACYW-TT vs. MCV4-TT. Seroprotection and seroresponse were higher in MenC-naïve participants vaccinated with MenACYW-TT vs. MCV4-TT and comparable in MenC-primed. The safety profiles were comparable between groups and no new safety concerns were identified. CONCLUSIONS: These data support the concomitant administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines in adolescents. TRIAL REGISTRATIONS: Clinicaltrials.gov, NCT04490018; EudraCT: 2020-001665-37; WHO: U1111-1249-2973.

MenACYW conjugate vaccine has been made to protect against meningococcal disease caused by four common types of bacteria (germs) called Neisseria meningitidis (or meningococcus), A, C, W, and Y. Many people, particularly adolescents, have the germs of this disease in their nose or throat, and therefore may develop the disease or transmit the bacteria to other people. Hence, adolescent meningococcal vaccination against serogroups ACWY is increasingly recommended in several countries. This study assessed the immune response to these serogroups in healthy adolescents after one dose of MenACYW conjugate vaccine or Nimenrix^®, a meningococcal licensed vaccine. Moreover, the immune response and safety were assessed when the vaccines were given alone or when given concomitantly with other adolescent vaccines, including the human papillomavirus (9vHPV) and tetanus, diphtheria, pertussis, and poliomyelitis (Tdap-IPV) vaccines. A total of 463 adolescents (aged 10­17 years) participated in this study and received either MenACYW or Nimenrix^® alone, or MenACYW concomitantly with 9vHPV and Tdap-IPV vaccine. The immune response induced by MenACYW was as good as the immune response induced by Nimenrix^®, and when given alone or concomitantly with 9vHPV and Tdap IPV vaccines. None of the participants experienced any serious side effects of any vaccine. The most common non-serious side effects were injection site pain, muscle pain, and headache. These data support the use of MenACYW in adolescents, with or without concomitant administration with 9vHPV and Tdap-IPV, which may help to increase the number of adolescents vaccinated.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT): A review of the evidence and expert opinion.

INTRODUCTION: Serogroups A, B, C, W, X, and Y of Neisseria meningitidis are responsible for almost all cases of invasive meningococcal disease. In Italy, vaccination against serogroup B is recommended at 3-13 months, C at 13-15 months, and A, C, Y and W in adolescents (12-18 years). Four quadrivalent meningococcal conjugate vaccines are available. This review describes the available data on a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT; MenQuadfi®; Sanofi). AREAS COVERED: We identified articles on quadrivalent meningococcal conjugate vaccines indexed on PubMed since 2000. Of the 524 studies identified, 10 human studies investigating the immunogenicity and safety of MenACYW-TT in toddlers, children aged 2-9 years, and individuals 10-55 or ≥56 years are described in detail. EXPERT OPINION: In Italy, pediatric and public health groups recommend amending the current vaccination schedule to include a booster dose between 6 and 9 years and quadrivalent vaccine in young adults (≥19 years), targeting waning protection after childhood vaccination and the age cohort with the highest carrier prevalence (adolescents and young adults). MenACYW-TT is a suitable meningococcal vaccine for current and pending recommendations based on high seroprotection rates and a low incidence of adverse events in these age groups. Moreover, it does not require reconstitution.

Immunogenicity and Safety of a Quadrivalent Meningococcal Tetanus Toxoid-Conjugate Vaccine (MenACYW-TT) in Meningococcal Vaccine-Naïve Participants across a Broad Age Range (2-55 Years) in Japan: a Phase III Randomized Study.

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 with MCV4-DT, a licensed meningococcal quadrivalent diphtheria-conjugate vaccine. This Phase III double-blind, multicenter trial was conducted in meningococcal vaccine-naïve individuals aged 2-55 years in Japan (NCT04368429; jRCT2080225192). Participants were randomized 1:1 to receive either 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 a post-vaccination titer ≥1:16 in participants with a baseline titer <1:8; or a ≥4-fold increase in titer in participants with a baseline titer ≥1:8. Safety data were collected for 30 days. Non-inferiority of the seroresponse to MenACYW-TT vs. MCV4-DT was demonstrated on D30 for each serogroup tested (A: 85.6% vs. 65.4%; C: 96.6% vs. 62.6%; W: 87.4% vs. 49.2%; Y: 97.7% vs. 63.5%). MenACYW-TT was well tolerated with no safety concerns identified. A single dose of MenACYW-TT was well tolerated, with a non-inferior seroresponse compared with MCV4-DT. MenACYW-TT could thus be used as an alternative vaccine in meningococcal vaccine-naïve individuals.

Structured Benefit-Risk Assessment of a New Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Individuals Ages 12 Months and Older.

INTRODUCTION: A favorable benefit-risk balance is required to support licensure of biologics, in keeping with regulatory agencies' evolving recommendations, including the United States Food and Drugs Administration. We present a structured semi-quantitative benefit-risk analysis of MenACYW-TT, a quadrivalent meningococcal conjugate vaccine against Neisseria meningitidis serogroups, A, C, W and Y versus licensed comparators in individuals aged ≥ 12 months. METHODS: We used data from six MenACYW-TT clinical trials, stratified by age group, versus licensed vaccines: toddlers (12-23 months; Nimenrix® [MCV4-TT]), children (2-9 years; Menveo® [MCV4-CRM]), adolescents (10-17 years; MCV4-CRM or Menactra® [MCV4-DT]), adults (18-55 years; MCV4-DT) and older adults (≥ 56 years; Menomune®-A/C/Y/W-135 [MPSV4]). Eight benefit (seroresponse and seroprotection for A, C, W and Y) and five risk outcomes (any and grade 3 solicited injection site and systemic reactions, and serious adverse events) were measured at Day 30 after initial vaccination. Analyses were conducted by baseline vaccination status (meningococcal vaccine-naïve or vaccine-primed). RESULTS: MenACYW-TT showed favorable seroresponse and seroprotection among vaccine-naïve participants aged ≥ 2 years, against all serogroups, compared with MCV4-CRM, MCV4-DT and MPSV4. In vaccine-naïve toddlers, there was a favorable effect for serogroup C, but no difference between MenACYW-TT and MCV4-TT for serogroups A, Y and W. A favorable effect for MenACYW-TT against serogroup C was observed in all vaccine-naïve and combined vaccine-naïve and MenC conjugate vaccine-primed groups. For all risk criteria, there were no differences between MenACYW-TT and MCV4s in toddlers, children, adolescents and adults. Results for solicited injection site and systemic reactions favored MPSV4 in older adults. CONCLUSIONS: The benefit-risk profile for MenACYW-TT showed favorable seroresponse and seroprotection in individuals aged ≥ 2 years and no difference in risk criteria between MenACYW-TT and MCV4s. MenACYW-TT may provide an alternative to the standard-of-care for meningococcal disease prevention in those aged ≥ 12 months.

Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered as a booster to adults aged ≥59 years: A phase III randomized study.

This 2-stage Phase III study (NCT04142242) of a recently licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) assessed the safety and immunogenicity of a booster dose in older adults (≥59 years) primed with either MenACYW-TT or a quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immune persistence of MenACYW-TT and MPSV4 after primary vaccination was also evaluated. During Stage I, the participants administered MPSV4 (n = 165) or MenACYW-TT (n = 236) 3 years previously were randomized 9:2 to receive either a MenACYW-TT booster or to have blood drawn for persistence only. Participants primed with MPSV4 or MenACYW-TT 6-7 years previously had blood drawn for antibody persistence only. A serum bactericidal assay using human complement was used to measure functional antibodies against each serogroup at baseline and, for those receiving a booster, 30 days post-vaccination (D30). Proportions of participants with seroresponse (post-vaccination titers ≥1:16 when baseline titers <1:8 or ≥ 4-fold increase when baseline titers ≥1:8) were determined. Safety data were collected up to D30. Seroresponse rates for all serogroups at D30 ranged from 49.2% to 60.8% in the MPSV4-primed group, and 79.3-93.1% in the MenACYW-TT-primed group. MenACYW-TT induced sufficient seroresponses in each primed group. Geometric mean titers (GMTs) for serogroups C, W, and Y remained or trended higher than pre-vaccination levels at both 3 and 6-7 years after primary vaccination, indicating immune persistence. Safety outcomes were comparable between groups. A MenACYW-TT booster was immunogenic and well tolerated in participants aged ≥59 years regardless of previous quadrivalent meningococcal vaccine received. The greatest immune responses occurred in those primed with MenACYW-TT.

Immunogenicity and safety of an investigational quadrivalent meningococcal conjugate vaccine administered as a booster dose in children vaccinated against meningococcal disease 3 years earlier as toddlers: A Phase III, open-label, multi-center study.

Booster doses of meningococcal conjugate vaccines induce long-term protection against invasive meningococcal disease. We evaluated the immunogenicity and safety of a booster dose of MenACYW-TT in pre-school children who were primed 3 years earlier with MenACYW-TT or MCV4-TT (Nimenrix®). In this Phase III, open-label, multi-center study (NCT03476135), children (4-5 years old), who received a primary dose of MenACYW-TT or MCV4-TT as toddlers in a previous study, received a booster dose of MenACYW-TT. Titers of antibody against meningococcal serogroups A, C, W and Y were measured by serum bactericidal assay using human (hSBA) and baby rabbit (rSBA) complement in samples collected before (D0) and 30 days after (D30) booster vaccination. Safety was assessed over the 30-day study period. Ninety-one participants received the booster dose. In both study groups, hSBA titers increased from D0 to D30; serogroup C titers [95% confidence interval] were higher in the MenACYW-TT-primed vs MCV4-TT-primed group at D0 (106 [73.2, 153] vs 11.7 [7.03, 19.4], respectively) and D30 (5894 [4325, 8031] vs 1592 [1165, 2174], respectively); rSBA results were similar. Nearly all participants achieved ≥1:8 hSBA and rSBA titers at D30, which were higher or comparable to those observed post-primary dose, suggesting rapid booster responses. At D0, all hSBA and rSBA titers were higher than those observed pre-primary dose, suggesting persistence of immunogenicity. The MenACYW-TT booster dose was well-tolerated and had similar safety outcomes across study groups. These findings suggest that MenACYW-TT elicits robust booster responses in children primed 3 years earlier with MenACYW-TT or MCV4-TT.

A Mouse Immunogenicity Model for the Evaluation of Meningococcal Conjugate Vaccines.

The identification of an appropriate animal model for use in the development of meningococcal vaccines has been a challenge as humans are the only natural host for Neisseria meningitidis. Small animal models have been developed and are widely used to study the efficacy or immunogenicity of vaccine formulations generated against various diseases. Here, we describe the development and optimization of a mouse model for assessing the immunogenicity of candidate tetravalent meningococcal polysaccharide (MenACYW-TT) protein conjugate vaccines. Three inbred (BALB/c [H-2d], C3H/HeN [H-2k], or C57BL/6 [H-2b]) and one outbred (ICR [H-2g7]) mouse strains were assessed using serial two-fold dose dilutions (from 2 µg to 0.03125 µg per dose of polysaccharide for each serogroup) of candidate meningococcal conjugate vaccines. Groups of 10 mice received two doses of the candidate vaccine 14 days apart with serum samples obtained 14 days after the last dose for the evaluation of serogroup-specific anti-polysaccharide IgG by ELISA and bactericidal antibody by serum bactericidal assay (SBA). C3H/HeN and ICR mice had a more dose-dependent antibody response to all four serogroups than BALB/c and C57Bl/6 mice. In general, ICR mice had the greatest antibody dose-response range (both anti-polysaccharide IgG and bactericidal antibodies) to all four serogroups and were chosen as the model of choice. The 0.25 µg per serogroup dose was chosen as optimal since this was in the dynamic range of the serogroup-specific dose-response curves in most of the mouse strains evaluated. We demonstrate that the optimized mouse immunogenicity model is sufficiently sensitive to differentiate between conjugated polysaccharides, against unconjugated free polysaccharides and, to degradation of the vaccine formulations. Following optimization, this optimized mouse immunogenicity model has been used to assess the impact of different conjugation chemistries on immunogenicity, and to screen and stratify various candidate meningococcal conjugate vaccines to identify those with the most desirable profile to progress to clinical trials.

Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study.

BACKGROUND: The MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks-15 months of age). METHODS: Five schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone. Routine pediatric vaccines (DTaP-IPV/Hib, PCV7/PCV13, MMR, and varicella) were administered per approved schedules. Proportions of participants with serum bactericidal antibodyassay with human complement (hSBA) titers ≥1:4 and ≥1:8, SBA with baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128, and immune responses against concomitant vaccines were determined. RESULTS: Tenderness and irritability were the most frequent solicited injection site and systemic reactions. Similar proportions of participants achieved an hSBA titer ≥1:8 for all four serogroups regardless of whether 2 or 3 doses were administered in the first year of life. Following a second-year dose, 91-100% of participants achieved the threshold for all 4 serogroups in all schedules regardless of the number of doses in the first year of life. Similar responses were seen with rSBA. Immunogenicity and safety profile of concomitant vaccines was similar whether the MenACYW-TT conjugate vaccine was administered or not. CONCLUSION: MenACYW-TT conjugate vaccine administered with pediatric vaccines is safe and immunogenic regardless of the schedule and does not affect the immunogenicity or safety of the concomitant vaccines. CLINICAL TRIAL REGISTRY: NCT01049035.

Immunogenicity and safety of MenACWY-TT, a quadrivalent meningococcal tetanus toxoid conjugate vaccine recently licensed in the United States for individuals ≥2 years of age.

Vaccination offers the best way to prevent invasive meningococcal disease (IMD). As demonstrated in countries with national immunization programs (NIPs) against IMD, meningococcal conjugate vaccines have contributed to significant declines in incidence. Since some meningococcal vaccines are associated with modest immunogenicity in infants, possible immunological interference upon concomitant administration with some pediatric vaccines, and administration errors resulting from improper reconstitution, opportunities for improvement exist. A quadrivalent conjugate vaccine, MenQuadfi® (Meningococcal [Serogroups A, C, Y, and W] Conjugate Vaccine; Sanofi, Swiftwater, Pennsylvania), was approved in 2020 for the prevention of IMD caused by meningococcal serogroups A, C, W, and Y in individuals ≥2 years of age in the United States. Five pivotal studies and one ancillary study supported approval in the United States; clinical trials in infants are ongoing. Data on the immunogenicity and safety of this vaccine are presented, and its potential value in clinical practice is discussed.

Comparing the meningococcal serogroup C immune response elicited by a tetanus toxoid conjugate quadrivalent meningococcal vaccine (MenACYW-TT) versus a quadrivalent or monovalent C tetanus toxoid conjugate meningococcal vaccine in healthy meningococcal vaccine-naïve toddlers: A randomised, controlled trial.

MenACYW-TT (MenQuadfi®) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for use in individuals ≥12 months. This study assessed whether serogroup C immune responses with MenACYW-TT were at least non-inferior, or superior, to those of quadrivalent meningococcal ACWY (MCV4-TT; Nimenrix®) and monovalent meningococcal C (MenC-TT; NeisVac-C®) vaccines in toddlers (12-23 months). In this modified, double-blind Phase III study (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 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-naïve healthy toddlers the superiority of the MenACYW-TT serogroup C immune response versus MCV4-TT was demonstrated for hSBA GMTs (ratio 16.3 [12.7-21.0]) and seroprotection (difference 10.43% [5.68-16.20]); and versus MenC-TT in terms of rSBA GMTs (ratio 1.32 [1.06-1.64]). The safety profiles of a single dose of MenACYW-TT, MCV4-TT and MenC-TT were similar. In meningococcal vaccine-naïve 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.

A novel vaccine to prevent meningococcal disease beyond the first year of life: an early review of MenACYW-TT.

INTRODUCTION: Although quadrivalent meningococcal conjugate vaccines have been effective in preventing invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y across age groups from infants to adults, data on their efficacy and safety in adults ≥56 years of age are lacking. Moreover, multiple available quadrivalent conjugate vaccines require reconstitution prior to administration, introducing the potential for error. A novel quadrivalent meningococcal conjugate vaccine, MenACYW-TT (MenQuadfi®) was approved in 2020 for use in individuals ≥12 months of age as a single dose in the European Union and some other countries and in individuals ≥2 years of age in the United States. AREAS COVERED: The findings of Phase II/III studies that included >6600 individuals and evaluated the immunogenicity and safety of MenACYW-TT beyond the first year of life are comprehensively summarized and discussed. EXPERT OPINION: Extensive data on immunogenicity and safety, co-administration with routine vaccines, elicitation of robust booster responses, and significantly higher Men C responses versus monovalent MenC or MenACWY standard-of-care vaccines in toddlers suggest that MenACYW-TT may be suitable for inclusion in National Immunization Programs (NIPs) globally. The authors provide their perspectives on the clinical use of MenACYW-TT across age groups from toddlers through adults.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in healthy toddlers: a Phase II randomized study.

NEISSERIA MENINGITIDIS: can lead to invasive meningococcal disease to which young children are particularly vulnerable. We assessed the immunogenicity and safety of Sanofi Pasteur's investigational quadrivalent (serogroups A, C, Y, and W) meningococcal tetanus-toxoid conjugate vaccine, MenACYW-TT, as a single dose, in healthy meningococcal vaccine-naïve toddlers versus a licensed conjugate vaccine MCV4-TT (NCT03205358). In this Phase II study conducted in Finland, 188 toddlers aged 12-24 months were randomized 1:1 to MenACYW-TT or MCV4-TT. Serum bactericidal antibody assays using human complement (hSBA) and baby rabbit complement (rSBA) measured antibodies against each serogroup before and 30 days after vaccination. Participants were monitored for immediate adverse events (AEs) and post-vaccination AEs for 30 days. All analyses were descriptive. All 188 participants completed the study. The Day 30 hSBA seroresponses (hSBA titer <8 at baseline and post-vaccination titer ≥8, or ≥8 at baseline and ≥4-fold increase post-vaccination) were comparable between participants receiving MenACYW-TT (96.7-100%), and MCV4-TT (86.0-100.0%) for each serogroup. Most unsolicited AEs were of Grade 1 or Grade 2 intensity. There were no immediate hypersensitivity reactions, and no AEs or serious AEs leading to discontinuation from the study. In this exploratory study, MenACYW-TT vaccine was well tolerated and immunogenic. If confirmed in Phase III, a single dose of the MenACYW-TT vaccine may show promise as an alternative vaccine option for toddlers receiving meningococcal vaccination for the first time.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adults 56 years of age and older: a Phase II randomized study.

MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for the prevention of invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y in individuals aged 6 weeks and above. This Phase II, randomized, open-label, multicenter, exploratory study assessed the safety and immunogenicity of MenACYW-TT compared with a quadrivalent meningococcal polysaccharide vaccine (MPSV4) in 301 healthy adults aged ≥56 y in the US (NCT01732627). Participants were randomized 2:1 to receive MenACYW-TT or MPSV4. Serum bactericidal assays using human (hSBA) or baby rabbit (rSBA) complement were used to measure functional antibodies against meningococcal serogroups A, C, W, and Y at baseline and 30 d post-vaccination. Safety data were collected up to 30 d post-vaccination. Proportions of study participants with hSBA titers ≥1:8 against serogroups A, C, W, and Y were increased at Day 30 compared with baseline in both vaccine groups. The proportions of participants with hSBA titers ≥1:8 after MenACYW-TT vaccination were comparable to those after MPSV4 vaccination for serogroups A and C (A: 93.8% vs. 85.1%; C: 74.9% vs. 62.8%) and distinctly higher than after MPSV4 for serogroups W and Y (W: 79.5% vs. 60.6%; Y: 80.5% vs. 59.6%). Proportions of participants with rSBA titers ≥1:8 were comparable between vaccine groups for all four serogroups. The reactogenicity profiles of both vaccines were similar. Most unsolicited adverse events (AEs) were of Grade 1 or Grade 2 intensity, and no serious AEs were reported. The MenACYW-TT conjugate vaccine was well tolerated and immunogenic in adults aged ≥56 y.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in ≥56-year-olds: A Phase III randomized study.

BACKGROUND: Invasive meningococcal disease has a high mortality rate in individuals aged ≥56 years, but no vaccine is currently licensed in the USA for this age group. This study assessed the safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) compared with a meningococcal quadrivalent polysaccharide vaccine (MPSV4) in this age group. METHODS: This was a Phase III, modified double-blind, randomized, non-inferiority study (NCT02842866) across 35 clinical sites in the USA and Puerto Rico in individuals aged ≥56 years. A single dose of the MenACYW-TT (n = 451) or MPSV4 vaccine (n = 455) was administered on Day 0. A serum bactericidal assay with human (hSBA) and baby rabbit (rSBA) complement was used to measure antibodies against serogroups A, C, W, and Y test strains at baseline and Day 30. Safety data were collected up to six months post-vaccination. RESULTS: The seroresponse to MenACYW-TT was non-inferior to MPSV4 for each of the serogroups (A: 58.2% vs. 42.5%; C: 77.1% vs. 49.7%; W: 62.6% vs. 44.8%, Y: 74.4% vs. 43.4%, respectively). At Day 30, participants achieving hSBA titers ≥1:8 were higher for all serogroups after MenACYW-TT vs. MPSV4 (77.4-91.7 vs. 63.1-84.2%, respectively). No safety concerns were identified for either vaccine. CONCLUSION: MenACYW-TT was well-tolerated and immunogenic in ≥56-year-olds, offering the potential to replace MPSV4 in this age group.

Immunogenicity, safety and inter-lot consistency of a meningococcal conjugate vaccine (MenACYW-TT) in adolescents and adults: A Phase III randomized study.

BACKGROUND: MenACYW-TT is an investigational quadrivalent (serogroups A, C, W and Y) meningococcal conjugate vaccine that is being developed for protection against invasive meningococcal disease. METHODS: In this Phase 3, blinded, randomized study, 3344 meningococcal vaccine-naïve 10-55-year-olds were randomized (3:3:3:2) to receive one of three lots of MenACYW-TT or licensed quadrivalent meningococcal conjugate vaccine, MCV4-DT (NCT02842853). Antibody titers were assessed by human and rabbit complement serum bactericidal antibody assays. The co-primary objectives were to demonstrate lot-to-lot consistency of MenACYW-TT by the between-lot geometric mean titer ratios (GMTR) at Day 30, and non-inferiority of Day 30 vaccine seroresponses (titers ≥ 1:16 if pre-vaccination titers < 1:8, or ≥ 4-fold increase if pre-vaccination titers ≥ 1:8) with MenACYW-TT vs MCV4-DT. Further objectives included safety and immunogenicity. RESULTS: Lot consistency was demonstrated for all three lots, with GMTRs ranging from 0.87 to 1.1. The proportion of participants achieving seroresponse in the MenACYW-TT group (data pooled from the 3 lots) was non-inferior to MCV4-DT (A: 74% vs 55%; C: 89% vs 48%; W: 80% vs 61%; Y: 91% vs 73%, respectively). MenACYW-TT and MCV4-DT had similar safety profiles; no safety concerns were identified. CONCLUSIONS: The study met both co-primary endpoints, demonstrating lot-to-lot consistency and non-inferiority of MenACYW-TT vs MCV4-DT in adolescents and adults.

A Phase II, randomized, immunogenicity and safety study of a quadrivalent meningococcal conjugate vaccine, MenACYW-TT, in healthy adolescents in the United States.

BACKGROUND: MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for use in individuals ≥6 weeks of age. We evaluated the safety and immunogenicity of MenACYW-TT when compared to a licensed quadrivalent conjugate meningococcal vaccine (Menveo®; MCV4-CRM; GlaxoSmithKline, Italy), and when co-administered with tetanus, diphtheria, acellular pertussis (Tdap) and human papilloma virus (HPV4) vaccines in healthy meningococcal vaccine-naïve adolescents (10-17 years old) in the United States of America. METHODS: In this pivotal Phase II, open-label, multicenter study, 1715 participants were randomized to receive MenACYW-TT, MCV4-CRM, MenACYW-TT co-administered with Tdap and HPV4, or Tdap and HPV4 vaccines alone (NCT02199691). The primary objective was to evaluate whether antibody responses to MenACYW-TT antigens were non-inferior to antibody responses after MCV4-CRM administration. Meningococcal antibody titers were determined using human complement serum bactericidal assay (hSBA) with titers measured at baseline, and 30 days post vaccination (D30). A vaccine seroresponse was defined as baseline titers <1:8 with post-vaccination titers ≥1:8 or baseline titers ≥1:8 with a ≥4-fold increase at post-vaccination. Safety data were collected up to six months post-vaccination. RESULTS: Non-inferiority was demonstrated for MenACYW-TT vs MCV4-CRM (primary endpoint), and for MenACYW-TT co-administered with Tdap and HPV4 vs MenACYW-TT alone (secondary endpoint). The vaccine seroresponse rate was higher with MenACYW-TT than with MCV4-CRM, for each serogroup: A: 75.6% vs 66.4%; C: 97.2% vs 72.6%; W: 86.2% vs 66.6%; Y: 97.0% vs 80.8%. The safety profiles of MenACYW-TT, MCV4-CRM, and Tdap and HPV4 vaccines, administered with or without MenACYW-TT, were comparable. There were no vaccine-related serious adverse events. CONCLUSIONS: The MenACYW-TT vaccine was well tolerated and generated an immune response that was non-inferior to the licensed MCV4-CRM vaccine. Immunogenicity and safety profiles were comparable when MenACYW-TT was administered with or without Tdap and HPV4 vaccines in meningococcal vaccine-naïve adolescents.