, Swiftwater, PA), Mencevax (GlaxoSmithKline, Australia), and ACWY Vax (GlaxoSmithKline, Middlesex, UK) (Table 2). Multiple monovalent, bivalent, and quadrivalent conjugate meningococcal vaccines
C59 wnt have also been developed. Of these, two provide multivalent protection against serogroups A, C, Y, and W-135: a meningococcal diphtheria toxoid vaccine (Menactra, Sanofi Pasteur Inc.), and, most recently, a CRM197 oligosaccharide conjugate vaccine (ACWY-CRM; Menveo, Novartis Vaccines and Diagnostics, Cambridge, MA, USA).25–36 While vaccines that protect against disease caused by serogroups A, C, W-135, and Y are available, no licensed vaccine is currently available to protect generally against serogroup B. Recently approved in the
United States and the European Union for individuals aged 11 to 55 years, ACWY-CRM is a novel vaccine that has Selleck Dabrafenib also demonstrated effectiveness in young children and infants (<2 y) in phase II and phase III trials.37–39 In clinical studies, more individuals achieved a protective immune response [serum bactericidal assay using human complement (hSBA) titer ≥1 : 8 with ACWY-CRM] compared with MPSV4 and ACWY-D at 1 month postvaccination. As such, ACWY-CRM provides the potential for protection against meningococcal disease caused by serogroups A, C, W-135, and Y for the widest age range—from infants as young as 2 months to older adults.38,40,41 ACWY-CRM has been developed using oligosaccharides linked to the
carrier protein CRM197, a nontoxic mutant of diphtheria toxin. CRM197 has been shown to be useful as a protein carrier for several previously developed conjugate vaccines; it elicits a robust immune response in a broad range of age groups (including infants from 2 mo of age) and has a well-established safety profile.42 Studies have shown that vaccines incorporating CRM197 have contributed to significant declines in disease in countries implementing vaccination campaigns.43 CRM197 vaccines improve and prolong the immune response to bacterial polysaccharides by inducing Epothilone B (EPO906, Patupilone) high levels of bactericidal antibodies with high avidity, including in young infants.44 In adults, the immune response to ACWY-CRM is at least as robust as to ACWY-D and is superior for certain serogroups.41 A comparison study of ACWY-CRM with ACWY-D enrolled 1,359 adults aged 19 to 55 years. One month after vaccination with ACWY-CRM, the percentage of subjects with hSBA titer ≥1 : 8 was 69% to 94%, comparable to results observed with ACWY-D for A and W serogroups (A: 69% vs 70% and W: 94% vs 90%, respectively), and superior for serogroups C (80% vs 72%, respectively) and Y (79% vs 70%, respectively) (lower limit of the two-sided 95% CI >0%) (Figure 1). Levels of hSBA GMTs were superior with ACWY-CRM compared with ACWY-D for all serogroups except A, for which they were comparable.41 Similar results were observed using the composite endpoint of seroresponse.