Da. Alaaldeen et al., VACCINE POTENTIAL OF MENINGOCOCCAL FRPB - STUDIES ON SURFACE EXPOSUREAND FUNCTIONAL ATTRIBUTES OF COMMON EPITOPES, Vaccine, 12(6), 1994, pp. 535-541
Neisseria meningitidis expresses several novel outer membrane proteins
(OMPs) in vivo and when grown under iron limitation in vitro. One of
the most prominent is a 70 kDa ken-regulated protein (FrpB). FrpB was
purified by elution from SDS-polyacrylamide gels and rabbit polyclonal
antiserum (R-70) was raised against it. R-70 was bactericidal against
homologous, but not heterologous, strains in the presence of human co
mplement. The bactericidal activity was retained when R-70 was adsorbe
d with formaldehyde-fixed iron-replete cells (i.e. not expressing FrpB
), but lost when adsorbed with fixed iron-restricted cells (which expr
ess FrpB). A murine monoclonal anti-FrpB antibody (mAb M70) was raised
against a common epitope which showed complete cross-reaction on West
ern blots of OMPs from other serogroups and serotypes of N. meningitid
is and some commensal Neisseriae species. However, it failed to kill t
he organism. Immunogold electron microscopy on ultrathin sections, usi
ng the R-70 antiserum adsorbed with fixed iron-replete cells, showed l
abelling on 40% of the cells, whereas the R-70 adsorbed with fixed iro
n-restricted cells and mAb M70 failed to label. However, none of these
sera labelled whole cells, suggesting lack of surface accessibility.
It appears that the highly conserved cross-reactive epitopes of FrpB o
nly become exposed in the process of generating the antigen, whereas t
he surface-exposed epitopes recognized in killing assays are immunolog
ically variable among different strains. Therefore, despite the strong
immunogenicity of the common epitopes of FrpB in vivo, their apparent
lack of surface exposure and the failure of antibodies against them t
o kill meningococci do not support consideration of this protein alone
as the sole component of a broadly cross-protective vaccine.