title: Comparison and correlation of neisseria meningitidis serogroup B immunologic assay results and human antibody responses following three doses of the Norwegian meningococcal outer membrane vesicle vaccine MenBvac.
abstract: The prediction of efficacy of Neisseria meningitidis serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease.
authors.affiliation: Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Laboratory, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester, United Kingdom. jamie.findlow@hpa.org.uk
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: Audun
authors.initials: A
authors.lastname: Aase
authors.forename: Rachel
authors.initials: R
authors.lastname: Horton
authors.forename: Robert
authors.initials: R
authors.lastname: Heyderman
authors.forename: Jo
authors.initials: J
authors.lastname: Southern
authors.forename: Nick
authors.initials: N
authors.lastname: Andrews
authors.forename: Rita
authors.initials: R
authors.lastname: Barchha
authors.forename: Ewan
authors.initials: E
authors.lastname: Harrison
authors.forename: Ann
authors.initials: A
authors.lastname: Lowe
authors.forename: Emma
authors.initials: E
authors.lastname: Boxer
authors.forename: Charlotte
authors.initials: C
authors.lastname: Heaton
authors.forename: Paul
authors.initials: P
authors.lastname: Balmer
authors.forename: Ed
authors.initials: E
authors.lastname: Kaczmarski
authors.forename: Philipp
authors.initials: P
authors.lastname: Oster
authors.forename: Andrew
authors.initials: A
authors.lastname: Gorringe
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
mesh_terms: D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D001770:Blood Bactericidal Activity; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008875:Middle Aged; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D009664:Norway; D011817:Rabbits
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines