title: Comparison of phenotypically indistinguishable but geographically distinct Neisseria meningitidis Group B isolates in a serum bactericidal antibody assay.
abstract: The "gold standard" assay for measuring serologic protection against Neisseria meningitidis group B (MenB) is the serum bactericidal antibody (SBA) assay. Of vital importance to the outcome of the SBA assay is the choice of the target strain(s), which is often chosen on the basis of phenotype or genotype. We therefore investigated the effect on the results produced by the SBA assay of using phenotypically indistinguishable but geographically distinct MenB isolates. Nine PorA P1.19,15 and 11 PorA P1.7-2,4 MenB isolates were incorporated into the SBA assay using human complement and were assayed against sera obtained either before or after outer membrane vesicle vaccination. Large differences in the results produced by the isolates in the SBA assay were demonstrated. These included differences as great as 5.8-fold in SBA geometric mean titers and in the proportions of subjects with SBA titers of >/=4. Ranges of as many as 9 SBA titers were achieved by individual sera across the panels of isolates. To determine the reasons for the differences observed, investigations into the expression of capsular polysaccharide, PorA, PorB, Opc, and lipooligosaccharide (LOS) and into LOS sialylation were completed. However, minor differences were found between strains, indicating similar expression and no antigen masking. These results have implications for the choice of MenB target strains for inclusion in future studies of MenB vaccines and highlight the requirement for standardization of target strains between laboratories.
authors: Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Laboratory, Manchester Medical Microbiology Partnership, Clinical Sciences Building II, Manchester Royal Infirmary, Manchester, M13 9WZ, United Kingdom. jamie.findlow@hpa.org.uk
authors: Jamie
authors: J
authors: Findlow
authors: Ann
authors: A
authors: Holland
authors: Nick
authors: N
authors: Andrews
authors: Vincent
authors: V
authors: Weynants
authors: Franklin
authors: F
authors: Sotolongo
authors: Paul
authors: P
authors: Balmer
authors: Jan
authors: J
authors: Poolman
authors: Ray
authors: R
authors: Borrow
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D006801:Humans; D008589:Meningococcal Infections / Q000276:immunology* / Q000382:microbiology; D022401:Meningococcal Vaccines / Q000276:immunology; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology* / Q000302:isolation & purification; D015610:Serum Bactericidal Test
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines