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

The sequence H379-410 of the measles virus haemagglutinin (MV-H) protein fo rms a surface-exposed loop and contains three cysteine residues (Cys-381, C ys-386 and Cys-394) which are conserved among all measles isolates. It comp rises the minimal sequential B cell epitope (BCE) (H386-400) of the neutral izing and protective MAb BH6 that neutralizes all wild-type viruses tested. The aim of this study was to design synthetic peptides which induce neutra lizing antibodies against MV wild-type isolates. Peptides containing one or two copies of T cell epitopes (TCE) and BCEs of different lengths (H386-40 0, B-cc; H379-400, B-ccc), in different combinations and orientations were produced and iteratively optimized for inducing neutralizing antibodies. Pe ptides 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 ne utralized wild-type strains of different clades and geographic origins. Neu tralizing 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 s ubunit vaccines based on such peptides could potentially be used to activel y protect infants against wild-type viruses irrespective of persisting mate rnal antibodies.