A phase III clinical trial has recently been completed [22]. In summary, prior to June 2012, there was no vaccine licensed in the US for www.selleckchem.com/products/AZD6244.html the prevention of meningococcal disease in infants. The
combination of Nm serogroups C and Y polysaccharides together was specifically chosen for development to meet a need in the US for prevention of MenC and MenY IMD in infants and was manufactured together with Hib to obviate an additional injection at each infant vaccination [23]. The Vaccine HibMenCY-TT is a combination of three discrete polysaccharide–protein conjugates. Each 0.5 mL dose of HibMenCY-TT contains 2.5 μg of Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) and 5 μg each of MenC and MenY polysaccharide individually conjugated or bound to tetanus toxoid. The total amount of tetanus toxoid is approximately 17.75 μg. HibMenCY-TT does not contain adjuvant or preservative. HibMenCY-TT is supplied as a single-dose vial of lyophilized vaccine to be reconstituted with the accompanying vial of saline diluent [24]. Mechanism of Action Due to the low incidence of meningococcal disease, as for other novel meningococcal vaccines, efficacy trials of HibMenCY-TT were impractical and effectiveness was inferred based on demonstration of immunogenicity and achievement of presumed correlates of protection [25]. Serum bactericidal
activity (SBA) is a functional assay that measures killing of Nm by antibodies contained in the patient’s serum in the Tucidinostat solubility dmso presence of complement. The complement source may be human (hSBA) or rabbit PND-1186 nmr (rSBA). For hSBA, a titer of ≥4 is the accepted correlate of protection
for serogroup C based on clinical effectiveness [26]. For rSBA, a more conservative titer of ≥8 has been found to be most consistent with clinical efficacy of conjugate vaccines against serogroup C disease [25, 27]. Of note, this low bactericidal titer (with rabbit complement) does not necessarily indicate that bactericidal activity is the mechanism of immune protection (e.g., it may be a marker for an alternative mechanism such as human complement-enhanced opsonic antibody [28]). For serogroup Y, no true correlate of protection exists and the same hSBA and rSBA titers as for MenC have been accepted as surrogates of protection [27]. Due to the virtual mafosfamide elimination of Hib disease through routine vaccination, efficacy trials of novel Hib vaccines are not feasible. Effectiveness of the Hib polysaccharide in HibMenCY-TT was inferred based on comparative trials with other licensed Hib vaccines with non-inferiority of immunogenicity as the end-point. Based on an efficacy trial with Hib polysaccharide vaccine in Finland, it has been widely accepted that an anti-PRP antibody concentration of ≥0.15 μg/ml is adequate to confer short-term protection, and an anti-PRP concentration of ≥1.0 μg/ml is required for long-term protection (or protection for the following 12 months) [29, 30].