Investigational Quadrivalent Meningococcal Conjugate Vaccine Research Articles

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

ABSTRACT 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.

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.

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

BackgroundMenACYW-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. MethodsIn 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. ResultsNon-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. ConclusionsThe 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.

2724. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Healthy Meningococcal Vaccine-Naïve Children (2–9 Years)

BackgroundMenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine that contains tetanus toxoid as carrier protein. The vaccine is intended for global use in individuals 6 weeks of age and older. We evaluated the safety and immunogenicity of MenACYW-TT compared with a licensed quadrivalent conjugate meningococcal vaccine (MenACWY-CRM [Menveo®]) in US children 2–9 years of age.MethodsIn a modified double-blind Phase III study (NCT03077438), 1000 children were randomized to receive one dose of either MenACYW-TT vaccine or MenACWY-CRM vaccine. Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure antibodies against representative meningococcal serogroup strains at baseline and 30 days after vaccination. Safety data were collected up to 6 months post-vaccination.ResultsNon-inferiority of immune responses for all four serogroups, based on percentages of participants achieving hSBA vaccine seroresponse, was demonstrated for MenACYW-TT compared with MenACWY-CRM at Day 30 compared with baseline. The proportions of individuals with hSBA titers ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-CRM administration for all four serogroups (A: 86.4% vs 79.3%; C: 97.8% vs 67.1%; W: 94.8% vs 86.3%; Y: 98.5% vs 90.8%). Similar results were observed in two age substrata (2 to 5 years and 6 to 9 years). Percentages of participants with post-vaccination rSBA titers ≥ 1:128 were comparable between both groups. The safety profiles of MenACYW-TT and MenACWY-CRM were comparable. Reactogenicity at the MenACYW-TT injection site was lower than at the MenACWY-CRM injection site. There were no immediate adverse events (AEs), no AEs leading to study discontinuation, and no vaccine-related serious adverse events reported in the study.ConclusionMenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared with that for the licensed MenACWY-CRM vaccine when administered as a single dose to meningococcal vaccine-naïve children.Disclosures All authors: No reported disclosures.

1967. Study of the Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) When Co-administered with Other Vaccines in Healthy Adolescents

BackgroundThe MenACYW-TT conjugate vaccine is a quadrivalent meningococcal vaccine candidate intended for global use in all age groups. This pivotal phase II study evaluated the safety and immunogenicity of the vaccine when compared with a licensed quadrivalent conjugated meningococcal vaccine (MCV4-CRM) when co-administered with tetanus, diphtheria, acellular pertussis (Tdap), and human papilloma virus (HPV4) vaccines in meningococcal vaccine naïve adolescents (10–17 years of age).MethodsA randomized, open-label, multicenter study (NCT02199691) was conducted in 1,715 healthy subjects in the United States, who were randomly assigned to receive MenACYW-TT conjugate vaccine, MCV4-CRM, MenACYW-TT conjugate vaccine (co-administered with Tdap and HPV4), or Tdap and HPV4 vaccines. 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 30 days after vaccination. Safety data were collected up to 6 months post-vaccination.ResultsNoninferiority of immune response was demonstrated between MenACYW-TT conjugate vaccine and MCV4-CRM, and MenACYW-TT conjugate vaccine when co-administered with Tdap and HPV4 vaccines vs. when administered alone, based on percentages of study participants achieving hSBA vaccine seroresponse at Day 30 fromD0 baseline. The proportions of individuals with hSBA ≥ 1:8 after MenACYW-TT conjugate vaccine administration were higher than those after MCV4-CRM administration for all four serogroups (A: 93.5% vs. 82.8%; C: 98.5% vs. 76.0%; W: 99.1% vs. 90.7%; Y: 97.2% vs. 83.2%). Co-administration of MenACYW conjugate, Tdap and HPV4 vaccines did not generate any results suggestive of immune interference. Reactogenicity profiles were comparable across study groups. Most unsolicited adverse events were of Grade 1 or Grade 2 intensity. No vaccine related serious adverse events were reported.ConclusionMenACYW-TT conjugate vaccine was immunogenic and well tolerated when administered as a single dose to meningococcal vaccine naïve adolescents along with Tdap and HPV4 vaccines. Such a vaccine will offer an alternative for the prevention of invasive meningococcal disease in susceptible populations across the world.Disclosures All authors: No reported disclosures.

Randomized Trial on the Safety, Tolerability, and Immunogenicity of MenACWY-CRM, an Investigational Quadrivalent Meningococcal Glycoconjugate Vaccine, Administered Concomitantly with a Combined Tetanus, Reduced Diphtheria, and Acellular Pertussis Vaccine in Adolescents and Young Adults

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

Safety and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine after one or two doses given to infants and toddlers

With the emergence of multiple meningococcal serogroups in different geographic areas, broad vaccine protection from infancy is desirable. One hundred and seventy-five infants received either two doses of a meningococcal quadrivalent (A, C, W-135, Y) conjugate vaccine (MenACWY-CRM) at 6 and 12 months, one dose of MenACWY-CRM at 12 months, or MenC at 12 months and MenACWY-CRM at 18 months. Bactericidal antibody titers using human complement were measured before and 1 month after each dose. Injection-site reactions were reported by 22-45% of participants following MenACWY-CRM given at 6 or 12 months. Similar proportions of subjects had injection-site reactions following two doses of MenACWY-CRM (32-41%) or one dose of MenC (26-44%). The incidence of systemic adverse events was comparable between groups. After two doses of MenACWY-CRM, the percentages of participants reporting hSBA titers >or=8 were 100% for C, W-135, and Y, and 84% for A. Serogroup C titers were more than 10-fold higher after two doses of MenACWY-CRM than after one dose of MenC or MenACWY-CRM at 12 months. Serogroup C titers were comparable following a single dose of MenACWY-CRM or MenC at 12 months. MenACWY-CRM is well tolerated and immunogenic given at 12 months, or two doses at 6 and 12 months of age.

Chemistry of a new investigational quadrivalent meningococcal conjugate vaccine that is immunogenic at all ages

Meningococcal disease is a serious medical condition that can prove fatal within hours in otherwise healthy individuals. Disease incidence is highest in infants, yet there is no broadly protective quadrivalent vaccine that covers this age group. A new investigational quadrivalent meningococcal glycoconjugate vaccine against meningococcal serogroups A, C, W-135, and Y (MenACWY-CRM, Novartis Vaccines, Siena, Italy), has been developed to meet this medical need. This article discusses the vaccine technology behind MenACWY-CRM, focusing on the heritage of CRM 197, the conjugation chemistry, the sizing of the oligosaccharides, and the advantages that these may confer on the vaccine. We highlight the differences between available vaccines and look at the clinical experience with vaccines against other diseases, demonstrating the importance of each component to the immunogenicity of conjugate vaccines. The specific technological approach, including conjugation of meningococcal oligosaccharides of defined length to the CRM 197 protein, has led to a vaccine that has the potential to provide broad meningococcal protection against serogroups A, C, W-135, and Y for all ages.

Phase III Comparison of an Investigational Quadrivalent Meningococcal Conjugate Vaccine with the Licensed Meningococcal ACWY Conjugate Vaccine in Adolescents

Neisseria meningitidis is an important cause of invasive bacterial infection in the United States, and disease rates are higher for adolescents than for the general population. Quadrivalent meningococcal conjugate vaccine is recommended for routine vaccination of adolescents and high-risk groups. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, with the licensed meningococcal conjugate vaccine, Menactra. In this multicenter phase III study, 2180 adolescents 11-18 years of age were randomly assigned to 4 groups (1:1:1:1) to receive a single dose of 1 of 3 lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained before vaccination and 1 month after vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers after vaccination with MenACWY-CRM or Menactra were compared in noninferiority and superiority analyses. The hSBA geometric mean titers after MenACWY-CRM vaccination were higher than the hSBA geometric mean titers after Menactra vaccination, and criteria for superiority were met for this end point for all 4 serogroups. Also, the criteria for superiority of MenACWY-CRM, compared with Menactra, were met for the end points of proportion of subjects with postvaccination hSBA titers 1:8 and proportion of seroresponders for serogroups A, W-135, and Y. MenACWY-CRM was noninferior to Menactra for serogroup C for these end points. Reactogenicity was similar, with 64% of the MenACWY-CRM recipients and 70% of the Menactra recipients reporting mild and/or moderate solicited reactions. Neither vaccine was associated with a serious adverse event. MenACWY-CRM vaccine is well tolerated in adolescents and generates a stronger immune response than Menactra for all 4 serogroups. Clinicaltrials.gov identifier: NCT00450437 .