PROTECTION AGAINST MEASLES-VIRUS ENCEPHALITIS BY MONOCLONAL-ANTIBODIES BINDING TO A CYSTINE LOOP DOMAIN OF THE H PROTEIN MIMICKED BY PEPTIDES WHICH ARE NOT RECOGNIZED BY MATERNAL ANTIBODIES
D. Ziegler et al., PROTECTION AGAINST MEASLES-VIRUS ENCEPHALITIS BY MONOCLONAL-ANTIBODIES BINDING TO A CYSTINE LOOP DOMAIN OF THE H PROTEIN MIMICKED BY PEPTIDES WHICH ARE NOT RECOGNIZED BY MATERNAL ANTIBODIES, Journal of General Virology, 77, 1996, pp. 2479-2489
After immunization with measles virus (MV) several monoclonal antibodi
es (MAbs) were obtained, which reacted with peptides corresponding to
the amino acids 361-410 of the haemagglutinin protein (MV-H), Three of
these MAbs (BH6, BH21 and BH216) inhibited haemagglutination, neutral
ized MV in vitro and protected animals from a lethal challenge of rode
nt-adapted neurotropic MV, These MAbs reacted with the 15-mer peptides
H381 and H386 defining their overlapping region 386-395 as a sequenti
al neutralizing and protective epitope, which can be imitated by a sho
rt peptide, H381 and H386 share two Cys residues (C(386)KGKIQALC(394)E
NPEWA) and for optimal MAb binding of peptide (or MV) disulphide bonds
were required in addition to a linear C-terminal extension. Other MAb
s bound to peptides C- (BH147, BH195) and N-terminally (BH168, BH171)
adjacent to the loop but did not neutralize or protect, When sera from
measles patients or from women of childbearing age were tested with t
he peptides corresponding to this haemagglutinating and neutralizing e
pitope (HNE), none of the sera recognized the 15-mer peptides of this
region, while some reactivity was found to 30-mers homologous to diffe
rent wild-type mutants, Its lack of recognition by maternal antibodies
and its high degree of conservation would make the HNE loop an attrac
tive candidate to include into a subunit vaccine, which could be admin
istered during early childhood, independent of immune status.