When measured with C6-depleted match and added PMNs, the percentages of preimmunization sera with OP bactericidal titers of 1 1:5 in both vaccine organizations combined were 9% (3/32), 3% (1/31), and 16% (5/32) against strains H44/76, S3032, and NZ98/254, respectively
When measured with C6-depleted match and added PMNs, the percentages of preimmunization sera with OP bactericidal titers of 1 1:5 in both vaccine organizations combined were 9% (3/32), 3% (1/31), and 16% (5/32) against strains H44/76, S3032, and NZ98/254, respectively. of 1 1:5 were 3 to 16%, which increased to 55 to 72% ( 0.001 for each strain). Most postimmunization BA-positive sera were OP positive, but 10 to 37% of BA-negative sera also were OP positive. Comparing the two vaccine groups, there were no significant variations in the percentages of sera with BA or OP activity except for a higher percentage of OP against one strain in postimmunization sera from subjects in the combination vaccine group ( 0.02). The data support self-employed tasks for serum BA and OP bactericidal activity in safety against group B disease. Serum complement-mediated bactericidal activity (BA) was demonstrated by studies performed by Goldschneider et al. in the 1960s to confer safety against developing meningococcal disease (17). Subsequent studies also offered ample additional support for the protecting part of serum BA (2-4). However, the Goldschneider study also found that a negative serum BA titer of 1:4 did not necessarily forecast susceptibility to disease, since there were persons with bad titers who became colonized with the epidemic strain and who did not develop disease. However, despite additional data that bad MGCD-265 (Glesatinib) serum BA titers may underestimate the degree of immunity to meningococcal disease in the population (29, 30), a positive BA titer remains the only widely approved correlate of safety against meningococcal disease (5). The possible part of opsonophagocytosis (OP) in protecting persons with bad serum BA titers remains controversial, in part because individuals with deficiencies in terminal match pathway proteins, whose sera support OP but not BA, have a greatly improved risk of acquiring meningococcal disease (8, 9). The purpose of the present study was to investigate the potential self-employed tasks of serum BA and OP in conferring safety against group B meningococcal disease. To address this question, we developed an OP bactericidal assay that used normal human MGCD-265 (Glesatinib) being serum depleted of C6 as an exogenous match resource, which in the absence of polymorphonuclear leukocytes (PMNs) did not support serum BA. We used this assay to measure OP bactericidal activity of stored serum samples from adults who had been participants inside a earlier group B meningococcal vaccine trial. The respective sera also were assayed for BA using C6-adequate match, which in the absence of PMNs elicited bacteriolysis by formation of a membrane attack complex. (The MGCD-265 (Glesatinib) data were presented in part in the 15th International Pathogenic Neisseria Conference, September 2006, Cairns, Australia.) MATERIALS AND METHODS Serum samples. Stored serum samples were available from 32 subjects, aged 18 to 50 years, who had been immunized as part of a earlier vaccine trial. The subjects Rabbit Polyclonal to CSTL1 were from organizations that had been randomly assigned to receive an outer membrane vesicle (OMV) vaccine (= 17), which had been prepared by the Norwegian Institute of General public Health, Oslo (16), or the OMV vaccine combined with a recombinant protein (= 15) (21, 31). The study was performed under the direction of one of the authors (D. M. Granoff) and was conducted in the Pediatric Medical Research Center at Children’s Hospital and Study Center, Oakland. The recombinant protein, genome-derived neisserial antigen (GNA2132) (21) (encoded from the gene from strain 2996), was prepared by Chiron Vaccines, Siena, Italy (currently Novartis Vaccines). The dose of the OMV vaccine was 50 g per injection, and the dose of the combination vaccine was 25 g of OMV and 25 g of recombinant protein. Both vaccines were adsorbed with aluminium hydroxide (1.65 mg per injection). Subjects in both organizations were given three doses of vaccine, with each dose separated by a 1-month interval. The sera assayed in the present study were from all.