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 antibodies (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, neutralized MV in vitro and protected animals from a lethal challenge of rodent-adapted neurotropic MV. These MAbs reacted with the 15-mer peptides H381 and H386 defining their overlapping region 386-395 as a sequential neutralizing and protective epitope, which can be imitated by a short peptide. H381 and H386 share two Cys residues (C(386)KGKIQALC(394)ENPEWA) and for optimal MAb binding of peptide (or MV) disulphide bonds were required in addition to a linear C-terminal extension. Other MAbs bound to peptides C- (BH147, BH195) and N-terminally (BH 168, BH 171) adjacent to the loop but did not neutralize or protect. When sera from measles patients or from women of child-bearing age were tested with the peptides corresponding to this haemagglutinating and neutralizing epitope (HNE), none of the sera recognized the 15-mer peptides of this region, while some reactivity was found to 30-mers homologous to different wild-type mutants. Its lack of recognition by maternal antibodies and its high degree of conservation would make the HNE loop an attractive candidate to include into a subunit vaccine, which could be administered during early childhood, independent of immune status.
Laboratoire National de Santé, Luxembourg.
D
D
Ziegler
P
P
Fournier
G A
GA
Berbers
H
H
Steuer
K H
KH
Wiesmüller
B
B
Fleckenstein
F
F
Schneider
G
G
Jung
C C
CC
King
C P
CP
Muller
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001665:Binding Sites; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D003553:Cystine; D004220:Disulfides; D018792:Encephalitis, Viral / Q000517:prevention & control*; D018604:Epitope Mapping; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D008457:Measles / Q000517:prevention & control*; D008458:Measles Vaccine / Q000276:immunology*; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D004220:Disulfides; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; C032397:hemagglutinin protein G, measles virus; D003553:Cystine