770. The Role of Antibodies to Neisserial Heparin binding antigen (NHba) in Protection Elicited by the MenB-4C Vaccine
Session: Poster Abstract Session: Vaccines: Pediatric
Thursday, October 27, 2016
Room: Poster Hall
Posters
  • Final_EP_ID Week Poster.pdf (885.5 kB)
  • 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.

     

    Elizabeth Partridge, MD, MPH1, Serena Giuntini, PhD2, Eduardo Lujan, MS2 and Dan M. Granoff, MD2, (1)Pediatric Infectious Disease, UCSF Benioff Children's Hospital Oakland, Oakland, CA, (2)Children's Hospital and Research Institute, Oakland, CA

    Disclosures:

    E. Partridge, None

    S. Giuntini, None

    E. Lujan, None

    D. M. Granoff, None

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