Neutralization of measles virus wild-type isolates after immunization with a synthetic peptide vaccine which is not recognized by neutralizing passive antibodies.
The sequence H379-410 of the measles virus haemagglutinin (MV-H) protein forms a surface-exposed loop and contains three cysteine residues (Cys-381, Cys-386 and Cys-394) which are conserved among all measles isolates. It comprises the minimal sequential B cell epitope (BCE) (H386-400) of the neutralizing and protective MAb BH6 that neutralizes all wild-type viruses tested. The aim of this study was to design synthetic peptides which induce neutralizing antibodies against MV wild-type isolates. Peptides containing one or two copies of T cell epitopes (TCE) and BCEs of different lengths (H386-400, B(CC); H379-400, B(CCC)), in different combinations and orientations were produced and iteratively optimized for inducing neutralizing antibodies. Peptides with the shorter BCE induced sera that cross-reacted with MV but did not neutralize. The longer BCE containing the three cysteines (B(CCC)) and two homologous TCE were required for neutralization activity. These sera neutralized wild-type strains of different clades and geographic origins. Neutralizing serum was also obtained after immunization with human promiscuous TCEs. Furthermore B(CCC)-based peptides were fully immunogenic even in the presence of pre-existing MV-specific antibodies. The results suggest that subunit vaccines based on such peptides could potentially be used to actively protect infants against wild-type viruses irrespective of persisting maternal antibodies.
El Kasmi
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KC
Laboratoire National de Santé, PO Box 1102, L-1011 Luxembourg, Universität Tübingen, D-72076 Tübingen, Germany.
Fillon
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S
Theisen
D M
DM
Hartter
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H
Brons
N H
NH
Muller
C P
CP
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007223:Infant; D008297:Male; D008458:Measles Vaccine / Q000276:immunology / Q000494:pharmacology*; D008459:Measles virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D008458:Measles Vaccine; D014614:Vaccines, Synthetic