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

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.