Differences in surface expression of NspA among Neisseria meningitidis group B strains

NspA is a highly conserved membrane protein that is reported to elicit prot ective antibody responses against Neisseria meningitidis serogroups A, B an d C in mice (D. Martin, N. Cadieux, J, Hanel, and B. R. Brodeur, J. Exp. Me d. 185:1173-1183, 1997). To investigate the vaccine potential of NspA, we p roduced mouse anti-recombinant NspA (rNspA) antisera, which were used to ev aluate the accessibility of NspA epitopes on the surface of different serog roup B strains by an immunofluorescence flow cytometric assay and by suscep tibility to antibody-dependent, complement-mediated bacteriolysis. Among 17 genetically diverse strains tested, 11 (65%) were positive for NspA cell s urface epitopes and 6 (35%) were negative. All six negative strains also we re resistant to bactericidal activity induced by the anti-rNspA antiserum. In contrast, of the 11 NspA surface-positive strains, 8 (73%; P < 0.05) wer e killed by the antiserum and complement. In infant rats challenged with on e of these eight strains, the anti-rNspA antiserum conferred protection aga inst bacteremia, whereas the antiserum failed to protect rats challenged by one of the six NspA cell surface-negative strains. Neither NspA expression nor protein sequence accounted for differences in NspA surface accessibili ty, since all six negative strains expressed NspA in outer membrane prepara tions and since their predicted NspA amino acid sequences were 99 to 100% i dentical to those of three representative positive strains. However, the si x NspA cell surface-negative strains produced, on average, larger amounts o f group R polysaccharide than did the 11 positive strains (reciprocal geome tric mean titers, 676 and 224, respectively; P < 0.05), which suggests that the capsule may limit the accessibility of NspA surface epitopes. Given th ese strain differences in NspA surface accessibility, an rNspA-based mening ococcal B vaccine may have to be supplemented by additional antigens.