Serological basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: Reevaluation of correlates of protection

The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA), This may give higher titers tha n those obtained,vith human complement (hSBA), for which the "gold standard " correlate of protection for meningococcal C disease is a titer of greater than or equal to 4, Comparison of rSBA and hSBA titers in sera from unvacc inated adults with an rSBA titer of greater than or equal to 8 showed that for 93% (27 of 29) the titer was greater than or equal to 4 by hSBA, confir ming natural protection. Furthermore, sera from MCC vaccinees showed that a n rSBA titer of < 8 or <greater than or equal to> 128 discriminated suscept ibility and protection well (85% with rSBA titers of < 8 had hSBA titers of < 4, and 99% with rSBA titers of greater than or equal to 128 had hSBA tit ers of greater than or equal to 4). However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of greater than or equal to 4. In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre- and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose,vith, if available, evidence of antibody avidity maturation or an hSB A titer of result greater than or equal to 4. Applying these criteria to to ddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single do se of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64. In addition, of those with titers of < 128 post-MCC vaccination, 90% had titers of <greater than or equal to> 128 after a 10-mug polysaccharide booster dose, compared with only 7% of u nprimed age-matched toddlers given a full 50-mug dose. Furthermore, the inc rease in geometric mean avidity index pre- and postbooster was independent of post-primary MCC titer. These results indicated that the majority of tod dlers with an rSBA titer between 8 and 64, and some of those with an hSBA r esult of < 4, have mounted a protective immune response with the induction of immunological memory.