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.

Contribution of factor H-Binding protein sequence to the cross-reactivity of meningococcal native outer membrane vesicle vaccines with over-expressed fHbp variant group 1

“…This lack of linear correlation contrasts to what has been observed in adult humans for anti-DOMV IgG [41, 42] and anti-serogroup C capsule IgG [43]. Several factors may account for this difference: i) differences between human and murine immune system; ii) antibodies directed towards a wider range of antigens elicited by NOMV compared to DOMV; iii) the different nature of the antigens themselves, particularly in the case of MenC polysaccharide and fHbp (a polysaccharide and a protein, respectively).…”

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease

“…In summary, killing of meningococci by whole blood and/or plasma can be rapid (<1 hr), effective (≥99%) and was 4- to 6-fold more frequent than an SBA titer ≥1:4. Similar results were observed in earlier studies by other investigators using slightly different whole blood killing assays [48-51]. The data support the hypothesis that many adults with SBA titers <1:4 are immune from developing meningococcal disease.…”

Antibody persistence following MeNZB vaccination of adults and children and response to a fourth dose in toddlers

“…Bactericidal antibody decay in adults and adolescents in this study is similar to that demonstrated following three doses of the NIPH vaccine MenBvac 17 25. Following MenBvac, a titre ≥4 was demonstrated in 57% of English adults and 50% of Norwegian adults 12 months after three doses, and in 28% of Norwegian adolescents 10 months after three doses 17 19 25. Other experience using MeNZB demonstrated similar results in Norwegian adults of whom 60% had a titre ≥4 twelve months after three doses 19.…”

“…Although a variation in absolute bactericidal titres between laboratories was demonstrated, the proportion with a bactericidal antibody titre ≥1:4 remained relatively constant 14 22. Bactericidal antibody decay in adults and adolescents in this study is similar to that demonstrated following three doses of the NIPH vaccine MenBvac 17 25. Following MenBvac, a titre ≥4 was demonstrated in 57% of English adults and 50% of Norwegian adults 12 months after three doses, and in 28% of Norwegian adolescents 10 months after three doses 17 19 25.…”