Meningococcal Tetanus Toxoid Conjugate Vaccine Research Articles

1157. Immune Persistence and Booster Response of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) 5 Years After Primary Vaccination of Adults ≥59 Years of Age

Abstract Background MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It is approved for use in persons aged ≥2 years in the US and persons aged ≥1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. The second stage of a 2-stage study of MenACYW-TT, reported herein, evaluated immune persistence among older adults who received primary vaccination with either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT five years earlier at age ≥ 56 years. The immunogenicity and safety of a MenACYW-TT booster dose given to this population were also evaluated. Methods This was a Phase 3, 2-stage, randomized, open-label, multi-center study (NCT04142242) of adults aged ≥59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune persistence and response were assessed with a serum bactericidal assay using human complement (hSBA). Safety data were collected for up to 30 days after booster vaccination. All analyses were descriptive. Results Of the initial study population (N=471), 70 adults participated in Stage II of the study. At 5 years post-primary vaccination, seroprotection (hSBA ≥ 1:8) rates (SPRs) and hSBA geometric mean titers (GMTs) declined in both MenACYW-TT- and MPSV4-primed subjects, with SPRs and hSBA GMTs for serogroups A, C, W, and Y trending higher in MenACYW-TT- vs MPSV4-primed subjects (Table 1). Thirty days after booster vaccination, hSBA GMTs and SPRs increased from pre-booster for all serogroups and were, along with seroresponse rates, higher in MenACYW-TT-primed subjects compared to MPSV4-primed subjects (Table 2). Rates of AEs following booster vaccination were similar regardless of priming vaccine. No safety concerns were identified. Conclusion Five years after primary vaccination, immune persistence tended to be greater for MenACYW-TT vs MPSV4. A MenACYW-TT booster was well tolerated and immunogenic in adults ≥ 61 years, when administered 5 years after primary vaccination with either MPSV4 or MenACYW-TT. Disclosures Corwin A. Robertson, MD, MPH, FACP, Sanofi: Sanofi employee|Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Katherine Galarza, MD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Alexandre Selmani, PhD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Philipp Oster, MD, Sanofi: Sanofi employee

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

ABSTRACT 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.

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

ABSTRACT 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.

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

BackgroundThe 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). MethodsFive 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. ResultsTenderness 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. ConclusionMenACYW-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 registryNCT01049035.

1046. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered as a Booster to Adults ≥ 59 Years of Age

Abstract Background MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It was recently approved for use in persons aged ≥ 2 years in the US and persons aged ≥ 1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. This study evaluated seroresponse after a MenACYW-TT booster given to adults who received either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT three years earlier at age ≥ 56 years. Immune persistence up to 7 years after primary vaccination was also evaluated. Methods This was a Phase 3 randomized, open-label study (NCT04142242) of adults aged ≥ 59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune response and persistence were assessed with a serum bactericidal assay using human complement (hSBA). Sufficiency of the vaccine seroresponse was considered demonstrated if the lower limit of the 1-sided 97.5% CI for the percentage of subjects with an hSBA vaccine seroresponse against serogroups A, C, W and Y was &amp;gt; 40%. Safety data were collected up to 30 days after booster vaccination. Results A total of 471 persons were enrolled. Sufficiency of a MenACYW-TT booster was demonstrated for MPSV4- and for MenACYW-TT-primed subjects. hSBA seroresponse rates were higher among MenACYW-TT- vs MPSV4-primed subjects (79.3%–93.1% vs 49.2%–60.8%, respectively). Three to 7 years after primary vaccination, hSBA geometric mean titers (GMTs) and seroprotection rates (SPRs) declined in both MenACYW-TT- and MPSV4-primed subjects, with hSBA GMTs and SPRs for serogroups C, W, and Y generally remaining higher for MenACYW-TT- vs MPSV4-primed subjects; those for serogroup A were similar regardless of priming vaccine. Rates of adverse events following a MenACYW-TT booster were similar between MenACYW-TT- and MPSV4-primed subjects. No safety concerns were identified. Conclusion A MenACYW-TT booster was well tolerated and immunogenic when administered to either MPSV4- or MenACYW-primed adults aged ≥ 59 years. Up to 7 years after primary vaccination, immune persistence for serogroups C, W, and Y tended to be greater for MenACYW-TT vs MPSV4. Disclosures Corwin A. Robertson, MD, MPH, FACP, Sanofi Pasteur (Employee, Other Financial or Material Support, Stockholder) Alexandre Selmani, PhD, Sanofi Pasteur (Employee) Katherine Galarza, MD, Sanofi Pasteur (Employee) Philipp Oster, MD, Sanofi Pasteur (Employee, Stockholder)

14. Postmarketing Safety Experience With MenACWY-TT

BackgroundMenACWY-TT (Nimenrix®), a quadrivalent meningococcal tetanus toxoid conjugate vaccine, was first licensed in 2012 and is available in 82 countries but not in the United States. MenACWY-TT is administered in infants as a 2 + 1 (6 weeks to < 6 months of age) or 1 + 1 (6 to < 12 months of age) schedule with the booster dose at 12 months of age, and from 12 months of age as a single dose. In addition to its widespread use to protect against meningococcal serogroups A, C, W, and Y, MenACWY-TT is a constituent of an investigational pentavalent meningococcal (MenABCWY) vaccine currently undergoing clinical development. MethodsUsing the MenACWY-TT Periodic Safety Update Report (PSUR) with format and content in accordance with Good Pharmacovigilance Practice Module VII and International Council for Harmonisation Guideline E2C, for data up to April 19, 2020, postmarketing safety experience with MenACWY-TT is considered. The PSUR data included herein are spontaneous adverse events (AEs) from the Pfizer safety database. AEs were coded by system organ class (SOC) and preferred term (PT) using MedDRA v.22.1J. ResultsThe cumulative estimated exposure of MenACWY-TT was nearly 26 million doses, with the majority administered in 0- to 16-year-olds and in the Western European Union (Figure 1). Over the reporting period, 13,301 cumulative AEs occurred. The most common SOCs in the reporting period were general disorders and administration site conditions (n=5169; 39%); nervous system disorders (n=1986; 15%); injury, poisoning and procedural complications (n=1266; 10%); and gastrointestinal disorders (n=1031; 8%) (Figure 2). By PT, the most common AEs were pyrexia (n=1613; 12%), headache (n=738; 6%), and vaccination site pain (n=394; 3%) (Figure 3). Of the 3299 serious AEs reported, the most common were pyrexia (n=317; 10%) and headache (n=209; 6%). ConclusionBased on cumulative safety data in conjunction with existing efficacy and effectiveness data, the benefit-risk profile of MenACWY-TT remains favorable and is consistent with the safety profile of MenACWY-TT established in clinical studies. Disclosures Lidia Serra, MS, Pfizer Inc (Employee, Shareholder) Susan Mather, MD, Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Chris Webber, MD, Pfizer (Employee, Shareholder)

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

BackgroundInvasive 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. MethodsThis 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. ResultsThe 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. ConclusionMenACYW-TT was well-tolerated and immunogenic in ≥56-year-olds, offering the potential to replace MPSV4 in this age group.

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

ABSTRACT 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

ABSTRACT 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 booster dose of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adolescents and adults: a Phase III randomized study

ABSTRACT The quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) was assessed as a booster in this Phase III trial (NCT02752906). Quadrivalent meningococcal conjugate vaccine (MCV4)-primed individuals aged ≥15 y (n = 810) were randomized 1:1 to receive a single booster dose of MenACYW-TT (n = 403) or a licensed MCV4 (Menactra®; MCV4-DT [n = 407]). Serum bactericidal antibody assay with human complement (hSBA) was used to measure functional antibodies against serogroups A, C, W, and Y at baseline and Day 30 post-vaccination. Proportions of participants achieving seroresponse (post-vaccination titer ≥1:16 for those with baseline titer <1:8 or ≥4-fold increase in post-vaccination titer for those with baseline titer ≥1:8) were determined. Safety data were collected for 180 d post-vaccination. Non-inferiority of the immune response was demonstrated for MenACYW-TT compared with MCV4-DT based on the proportion of participants achieving hSBA vaccine seroresponse for each of the meningococcal serogroups at Day 30. Moreover, ≥99% of participants in both study groups had hSBA titers ≥1:8 for the four meningococcal serogroups at Day 30. Reactogenicity profiles were comparable between groups. These Phase III data in adolescents and adults show that MenACYW-TT boosts the immune response in those primed with MCV4 vaccines 4–10 y previously, irrespective of whether MCV4-DT or MCV4-CRM was used for priming.

Meningococcal Quadrivalent Tetanus Toxoid Conjugate Vaccine (MenACWY-TT; Nimenrix®): A Review.

MenACWY-TT (Nimenrix®) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for active immunisation of individuals aged ≥6 weeks against invasive disease caused by Neisseria meningitidis capsular groups A, C, W and Y. MenACWY-TT is the first quadrivalent conjugate vaccine to be approved in Europe for use in infants as young as 6weeks of age. Numerous phase II-IIIb clinical studies showed that intramuscular MenACWY-TT administered as primary or booster vaccination was highly immunogenic for all four vaccine capsular groups and had an acceptable reactogenicity profile in individuals aged 6 weeks to ≥56years. MenACWY-TT is as immunogenic and safe as other previously licensed monovalent capsular group C or quadrivalent capsular groups A, C, W and Y meningococcal vaccines and can be coadministered with other routine vaccines without adversely affecting the immunogenicity or safety profiles of either vaccine. Current data indicate that primary and booster vaccination with MenACWY-TT is a valuable and safe option for broadening meningococcal protection against four capsular groups across a broad age range, starting as early as 6weeks of age.

Meningococcal Polysaccharide A O -Acetylation Levels Do Not Impact the Immunogenicity of the Quadrivalent Meningococcal Tetanus Toxoid Conjugate Vaccine: Results from a Randomized, Controlled Phase III Study of Healthy Adults Aged 18 to 25 Years

In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ≥1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ≥1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.