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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.

Identifieur interne : 003E13 ( Main/Exploration ); précédent : 003E12; suivant : 003E14

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.

Auteurs : D. Ziegler [Luxembourg (pays)] ; P. Fournier ; G A Berbers ; H. Steuer ; K H Wiesmüller ; B. Fleckenstein ; F. Schneider ; G. Jung ; C C King ; C P Muller

Source :

RBID : pubmed:8887481

Descripteurs français

English descriptors

Abstract

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.

DOI: 10.1099/0022-1317-77-10-2479
PubMed: 8887481


Affiliations:


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Le document en format XML

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<name sortKey="Schneider, F" sort="Schneider, F" uniqKey="Schneider F" first="F" last="Schneider">F. Schneider</name>
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<name sortKey="Jung, G" sort="Jung, G" uniqKey="Jung G" first="G" last="Jung">G. Jung</name>
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<name sortKey="Berbers, G A" sort="Berbers, G A" uniqKey="Berbers G" first="G A" last="Berbers">G A Berbers</name>
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<name sortKey="Steuer, H" sort="Steuer, H" uniqKey="Steuer H" first="H" last="Steuer">H. Steuer</name>
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<name sortKey="Wiesmuller, K H" sort="Wiesmuller, K H" uniqKey="Wiesmuller K" first="K H" last="Wiesmüller">K H Wiesmüller</name>
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<name sortKey="Fleckenstein, B" sort="Fleckenstein, B" uniqKey="Fleckenstein B" first="B" last="Fleckenstein">B. Fleckenstein</name>
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<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Antibodies, Monoclonal (immunology)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Binding Sites</term>
<term>Cell Line, Transformed</term>
<term>Chlorocebus aethiops</term>
<term>Cystine</term>
<term>Disulfides</term>
<term>Encephalitis, Viral (prevention & control)</term>
<term>Epitope Mapping</term>
<term>Hemagglutinins, Viral (immunology)</term>
<term>Humans</term>
<term>Measles (prevention & control)</term>
<term>Measles Vaccine (immunology)</term>
<term>Measles virus (immunology)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
<term>Sequence Homology, Amino Acid</term>
<term>Vero Cells</term>
</keywords>
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<term>Animaux</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps monoclonaux (immunologie)</term>
<term>Cartographie épitopique</term>
<term>Cellules Vero</term>
<term>Cystine</term>
<term>Disulfures</term>
<term>Données de séquences moléculaires</term>
<term>Encéphalite virale ()</term>
<term>Humains</term>
<term>Hémagglutinines virales (immunologie)</term>
<term>Lignée de cellules transformées</term>
<term>Rougeole ()</term>
<term>Similitude de séquences d'acides aminés</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
<term>Vaccin contre la rougeole (immunologie)</term>
<term>Virus de la rougeole (immunologie)</term>
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<term>Antibodies, Monoclonal</term>
<term>Antibodies, Viral</term>
<term>Hemagglutinins, Viral</term>
<term>Measles Vaccine</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps monoclonaux</term>
<term>Hémagglutinines virales</term>
<term>Vaccin contre la rougeole</term>
<term>Virus de la rougeole</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Measles virus</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Encephalitis, Viral</term>
<term>Measles</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>Cell Line, Transformed</term>
<term>Chlorocebus aethiops</term>
<term>Cystine</term>
<term>Disulfides</term>
<term>Epitope Mapping</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
<term>Sequence Homology, Amino Acid</term>
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<term>Animaux</term>
<term>Cartographie épitopique</term>
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<term>Cystine</term>
<term>Disulfures</term>
<term>Données de séquences moléculaires</term>
<term>Encéphalite virale</term>
<term>Humains</term>
<term>Lignée de cellules transformées</term>
<term>Rougeole</term>
<term>Similitude de séquences d'acides aminés</term>
<term>Sites de fixation</term>
<term>Souris</term>
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<front>
<div type="abstract" xml:lang="en">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.</div>
</front>
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