A hemagglutinin-derived peptide-vaccine ignored by virus-neutralizing passive antibodies, protects against murine measles encephalitis

The neutralizing and protective monoclonal antibody BH47 defines the sequen tial epitope H236-255 of the measles virus hemagglutinin protein (MV-H). Th e objective of this study was to design peptides combining this B cell epit ope (BCE) with different T cell epitopes (TCE) to obtain protective immunit y. Most TTB peptides based on the 15mer BCE H236-250 induced MV-crossreacti ve antibodies, but only certain TCE induced virus neutralizing antibodies. The shortest BCE required for MV-reactivity and -neutralization was the 8me r H243-250 containing residue R-243 implicated in CD16 down-regulation. Ser a obtained after immunization with the TTB peptide containing the MV-derive d TCE F421-435 protected mice against a lethal challenge with a neuro-adapt ed MV strain. Our results further demonstrate that this TTB peptide is full y immunogenic, even in the presence of protective levels of pre-existing MV -specific antibodies, suggesting that subunit vaccines based on such peptid es could potentially be used to immunize infants in the presence of persist ing maternal antibodies. It is therefore interesting that neutralizing anti bodies were also obtained with a TTB peptide comprising a human promiscuous TCE (tt830). However, our results also emphasize the need to test sera ind uced with epitope-based vaccines against different virus strains, in partic ular if the epitope is not fully conserved. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.