Identification of an immunodominant neutralizing and protective epitope from measles virus fusion protein by using human sera from acute infection.
Polyclonal sera obtained from African children with acute measles were used to screen a panel of 15-mer overlapping peptides representing the sequence of measles virus (MV) fusion (F) protein. An immunodominant antigenic region from the F protein (p32; amino acids 388 to 402) was found to represent an amino acid sequence within the highly conserved cysteine-rich domain of the F protein of paramyxoviruses. Epitope mapping of this peptide indicated that the complete 15-amino-acid sequence was necessary for high-affinity interaction with anti-MV antibodies. Immunization of two strains of mice with the p32 peptide indicated that it was immunogenic and could induce antipeptide antibodies which cross-reacted with and neutralized MV infectivity in vitro. Moreover, passive transfer of antipeptide antibodies conferred significant protection against fatal rodent-adapted MV-induced encephalitis in susceptible mice. These results indicate that this epitope represents a candidate for inclusion in a future peptide vaccine for measles.
Atabani
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SF
Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, United Kingdom.
Obeid
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Chargelegue
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Aaby
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Whittle
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Steward
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D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D002459:Cell Fusion; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005714:Gambia; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008457:Measles / Q000097:blood / Q000276:immunology*; D008459:Measles virus / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D016415:Sequence Alignment; D013997:Time Factors; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000276:immunology*; D010948:Viral Plaque Assay
D000914:Antibodies, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D014760:Viral Fusion Proteins