The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C

Abstract

Background MenB-4C (Bexsero®) is a multicomponent serogroup B meningococcal vaccine. For vaccine licensure, efficacy was inferred from serum bactericidal antibody (SBA) against three antigen-specific indicator strains. The bactericidal role of antibody to the fourth vaccine antigen, Neisserial Heparin binding antigen (NHba), is incompletely understood. Methods We identified nine adults immunized with two or three doses of MenB-4C who had sufficient volumes of sera and >3-fold increases in SBA titer against a strain with high NHba expression, which was mismatched with the other three MenB-4C antigens that elicit SBA. Using 1 month-post-immunization sera we measured the effect of depletion of anti-NHba and/or anti-Factor H binding protein (FHbp) antibodies on SBA. Results Against three strains matched with the vaccine only for NHba, depletion of anti-NHba decreased SBA titers by an average of 43–79% compared to mock-adsorbed sera (P<0.05). Despite expression of sub-family A FHbp (mismatched with the subfamily B vaccine antigen), depletion of anti-FHbp antibodies also decreased SBA by 45–64% (P<0.05). Depletion of both antibodies decreased SBA by 84–100%. Against a strain with sub-family B FHbp and expression of NHba with 100% identity to the vaccine antigen, depletion of anti-NHba decreased SBA by an average of 26%, compared to mock-adsorbed sera (P<0.0001), and depletion of anti-FHbp antibody decreased SBA by 92% (P<0.0001). Conclusions Anti-NHba antibody can contribute to SBA elicited by MenB-4C, particularly in concert with anti-FHbp antibody. However, some high NHba-expressing strains are resistant, even with an exact match between the amino acid sequence of the vaccine and strain antigens.

Fatal Nongroupable Neisseria meningitidis Disease in Vaccinated Patient Receiving Eculizumab

“…Mouse anti-NHba antiserum had a titer of < 10. The relative resistance to anti-NHba was similar to previous findings that some NHba-expressing serogroup B meningococcal strains resist MenB-4C vaccine–elicited anti-NHba serum bactericidal activity (SBA) in humans ( 7 ).…”

The Neisseria gonorrhoeae Vaccine Candidate NHBA Elicits Antibodies That Are Bactericidal, Opsonophagocytic and That Reduce Gonococcal Adherence to Epithelial Cells

“…In addition to NHBA sequence and expression level, a combination of other factors is also likely to contribute to the SBA and OPA titres seen for different strains, including intrinsic strain features that can affect complement regulation and susceptibility of each strain to human serum used as a complement source. Similar intrinsic differences between strains have also been reported for anti-NHBA [34] and anti-fHbp bactericidal activity against N. meningitidis [35,36]. The SBA titres ranged from 50 to 1600 for the different vaccine antigens and formulations against different strains.…”

Synergic complement‐mediated bactericidal activity of monoclonal antibodies with distinct specificity

“…8,11,39 Previous studies demonstrated polyclonal sera targeting different meningococcal antigens can synergistically activate complement. 21,22 To investigate the molecular mechanisms involved in such synergy, we selected two well-known and characterized meningococcal antigens, fHbp and NHBA, as a model. The reason for this choice relies on the wide body of knowledge about the immunological properties of these two antigens.…”