The Role of Antibodies to Neisserial Heparin binding antigen (NHba) in Protection Elicited by the MenB-4C Vaccine

Background:  The GSK serogroup B meningococcal vaccine (MenB-4C) is composed of four components: outer membrane vesicles (OMV with PorA antigen serosubtype P1.4) and three recombinant proteins. One antigen, Factor H binding protein (FHbp), is classified into two sub-families, A and B.  Anti-FHbp serum bactericidal activity (SBA) is reported to be sub-family-specific. Since MenB-4C only contains sub-family B FHbp, protection against strains with sub-family A is thought to depend on antibodies to the other vaccine antigens, including Neisseria Heparin binding antigen (NHba).  However, the role of anti-NHba antibodies in SBA is incompletely understood.

Methods: From 18 adults immunized with MenB-4C, we selected five with ≥4-fold increases in SBA titers (Post/Pre) against a strain with high NHba expression (100% amino acid identity to the vaccine antigen) and mismatched for the other three vaccine antigens (i.e., sub-family A FHbp, absent NadA gene, and PorA other than P1.4). Post-immunization sera were depleted of anti-NHba or anti-FHbp antibodies by column adsorption. A 50% decrease in human complement-mediated SBA compared to mock-adsorbed sera was considered significant.

 

Results: Against a strain matched only for PorA P1.4, depletion of anti-FHbp or anti-NHba antibodies had no effect on SBA titers (consistent with OMV-induced SBA against PorA).  Against three strains matched with high NHba expression, and mismatched for the other antigens, serum anti-FHbp depletion decreased SBA more than anti-NHba depletion. Thus, despite strain sub-family A FHbp, cross-reacting sub-family B antibodies contributed to protection. Against a fifth strain mismatched for all 4 vaccine antigens, depletion of anti-FHbp decreased SBA by a mean of 62% while anti-NHba depletion had no effect (Left Panel). Against a sixth strain with sub-family B FHbp and high NHba expression, anti-FHbp depletion decreased SBA by mean of 82%, while anti-NHba depletion decreased the titer by a mean of 21% (Right panel).

Conclusion: MenB-4C coverage is predicted by strain expression and cross-reactivity of any of the four vaccine antigens. However, antibodies to sub-family B FHbp can protect against some strains with sub-family A FHbp. Further, only rarely did anti-NHba antibody alone have SBA.