A Decade of Fighting Invasive Meningococcal Disease: A Narrative Review of Clinical and Real-World Experience with the MenACWY-CRM Conjugate Vaccine

Abstract

The quadrivalent A, C, W and Y meningococcal vaccine conjugated to nontoxic mutant of diphtheria toxin (MenACWY-CRM) has been licensed since 2010 for the prevention of invasive meningococcal disease (IMD), an uncommon but life-threatening condition. Here, we summarize the experience accrued with MenACWY-CRM during the first decade since its licensure, by providing an overview of clinical trials investigating the safety, immunogenicity and co-administration of MenACWY-CRM with other vaccines as well as presenting real-world evidence regarding the impact of MenACWY-CRM vaccination on carriage and IMD incidence. MenACWY-CRM has demonstrated an acceptable clinical safety profile across a wide range of age groups; no safety concerns have been reported in special populations, such as immunocompromised infants and toddlers, or pregnant women. MenACWY-CRM has also been proven to be immunogenic in various age groups and geographic settings, and a booster dose has been shown to elicit strong anamnestic responses in all studied populations, irrespective of the vaccine used for priming. With no clinically relevant vaccine interactions reported, MenACWY-CRM is being conveniently integrated into existing vaccination programs for various age and risk groups; this possibility of co-administration helps improving vaccine coverage and streamlining the healthcare process of fighting preventable infectious diseases. Vaccination of adolescents and adults has been proven to reduce nasopharyngeal carriage for serogroups C, W and Y, which is an important element in reducing transmission. Real-world evidence indicates that MenACWY-CRM can reduce IMD incidence even in high-exposure groups. When combined with vaccines against serogroup B meningococci, MenACWY-CRM can offer protection against five of the most common serogroups responsible for IMD, which is an important advantage in the continuously evolving landscape of meningococcal serogroup epidemiology. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00519-2.

Fully Liquid MenACWY-CRM Vaccine: Results from an Integrated Safety Analysis

“…None of the SAEs were considered related to vaccination and there were no study withdrawals due to an AE. Altogether, the data from this large pooled analysis are consistent with the documented safety profile of the licensed MenACWY-CRM vaccine [6,7,15]. Moreover, while the aim of this safety analysis was only to compare two presentations of the same vaccine, indirect comparisons show that, overall, the clinical tolerability and safety profile of the fully liquid MenACWY-CRM vaccine evaluated in the two phase 2b clinical studies also appears comparable with that reported for fully liquid presentations of other licensed MenACWY conjugated vaccines (including as carrier diphtheria toxoid or tetanus toxoid) [16,17].…”

“…Numerous clinical trials have demonstrated the robust immunogenicity of MenACWY-CRM in various age groups and its clinical tolerability and safety profile was shown to be similar to that of a plain polysaccharide vaccine [ 7 , 14 ]. Additionally, the acceptable safety profile of MenACWY-CRM has been confirmed in large post-marketing safety studies [ 6 ].…”

“…Additionally, the acceptable safety profile of MenACWY-CRM has been confirmed in large post-marketing safety studies [ 6 ]. The most frequent solicited AEs overall in older children, adolescents, and adults in the clinical trials were injection site pain, headache, and myalgia [ 6 , 7 ]. In our integrated safety analysis, the most frequent solicited AEs in both vaccine groups were injection site pain, headache, and fatigue in the overall population and in the two age groups analyzed, with similar frequencies of each solicited AE between vaccine groups.…”

“…The single-vial liquid MenACWY-CRM presentation contains the same amount of antigen as the licensed presentation, the main difference being the absence of sucrose and potassium dihydrogen phosphate in the fully liquid presentation, which is included as lyophilization matrix for the MenA component of the licensed vaccine and is therefore not needed for the new liquid presentation. Numerous clinical trials have demonstrated the robust immunogenicity of MenACWY-CRM in various age groups and its clinical tolerability and safety profile was shown to be similar to that of a plain polysaccharide vaccine [7,14]. Additionally, the acceptable safety profile of MenACWY-CRM has been confirmed in large post-marketing safety studies [6].…”

“…The quadrivalent glycoconjugate vaccine MenACWY-CRM ( Menveo , GSK) was first licensed in 2010 and has a well-established safety and immunogenicity profile [ 6 , 7 ]. The vaccine uses non-toxic diphtheria cross-reacting material 197 (CRM 197 ) as carrier protein, conjugated to MenA, MenC, MenW, and MenY polysaccharides.…”