The Development of a Mimotope-based Synthetic Peptide Vaccine Against Respiratory Syncytial Virus

Abstract

Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children worldwide and the development of a synthetic peptide epitope-based vaccine to induce virus-neutralising antibodies against RSV would seem to be a valid approach to the production of an effective vaccine against infection.A combinatorial solid-phase peptide library has been screened with a virus-neutralising, protective monoclonal antibody (MAb19) directed towards a conserved and conformationally-determined epitope of the Fusion (F) protein of the virus. Two of the sequences identified from the peptide library using MAb19 reacted specifically with the antibody and amino acid substitution experiments identified four sequences from one of the mimotopes which showed increased reactivity with MAb19.Immunisation of BALB/c mice with these mimotopes, presented as MAPs, resulted in the induction of anti-peptide antibodies that inhibited the binding of MAb19 to the virus and neutralised viral infection in vitro, with titres equivalent to those in sera from RSV-infected animals. Following RSV challenge of mimotope-immunised mice, a significant reduction in the titre of virus and a greatly reduced cell infiltration into the lungs of immunised mice compared to that in controls was observed.The induction of virus-specific cytotoxic T-lymphocyte responses as well as virus-specific antibodies are likely to be necessary in an effective vaccine. The incorporation of a peptide representing a CTL epitope from the M2 protein of the virus together with peptides inducing T-helper and anti-mimotope responses in a peptide cocktail vaccine resulted in a more effective clearance of the virus from immunised, challenged mice than peptide-induced humoral or cellular immunity alone.