Neutralization of measles virus wild-type isolates after immunization with a synthetic peptide vaccine which is not recognized by neutralizing passive antibodies

J Gen Virol. 2000 Mar;81(Pt 3):729-35. doi: 10.1099/0022-1317-81-3-729.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Antibodies, Viral / blood*
  • Antigens, Viral / genetics
  • B-Lymphocytes / immunology
  • Cross Reactions
  • Epitopes / genetics
  • Female
  • Humans
  • Immunization, Passive
  • Infant
  • Male
  • Measles Vaccine / immunology
  • Measles Vaccine / pharmacology*
  • Measles virus / genetics
  • Measles virus / immunology*
  • Measles virus / isolation & purification
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neutralization Tests
  • T-Lymphocytes / immunology
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / pharmacology*

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Epitopes
  • Measles Vaccine
  • Vaccines, Synthetic