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

Judith Kirstein,Miriam Pina,Judy Pan,Emilia Jordanov,Mandeep S Dhingra

doi:10.1080/21645515.2020.1733868

Judith Kirstein, Miriam Pina + Show 3 more

Open Access

https://doi.org/10.1080/21645515.2020.1733868

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Abstract

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.

Highlights

Invasive meningococcal disease (IMD) is a rapid-onset invasive bacterial disease with potentially life-changing consequences.[1]
All participants demonstrated a marked increase in both hSBA and rSBA titers 30 d after vaccination with either MenACYW-TT or MPSV4, and the differences seen between assays are consistent with previous observations of the limited correlation between assays.[19,20,21]
The overall safety profile was comparable across both vaccine groups, with no new safety concerns reported during the duration of the study

Summary

Introduction

Invasive meningococcal disease (IMD) is a rapid-onset invasive bacterial disease with potentially life-changing consequences.[1] IMD is caused by Neisseria meningitidis, a Gram-negative diplococcus found exclusively in humans. It is associated with a high rate of mortality, with a casefatality rate of approximately 10%.2. N. meningitidis has been classified into at least 12 distinct meningococcal serogroups,[3] six of which (A, B, C, W, Y, and X) have been identified as responsible for the majority of global IMD cases.[4,5] Despite a number of effective licensed vaccines available, N. meningitidis remains a leading cause of bacterial meningitis and septicemia on a global scale.[5,6]. The case-fatality rate of IMD is highest in adults aged ≥65 y.8,12,13

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