Induction of high titred, non-neutralising antibodies by self-adjuvanting peptide epitopes derived from the respiratory syncytial virus fusion protein

Noushin Jaberolansar, Keith J. Chappell, Daniel Watterson, Imogen M. Bermingham, Istvan Toth, Paul R. Young, Mariusz Skwarczynski

Respiratory syncytial virus (RSV) causes severe lower respiratory tract illness in infants and young children. The significant morbidity and mortality rates associated with RSV infection make an effective RSV vaccine development a priority. Two neutralising antibody binding sites, Ø and II, located on the pre-fusion RSV F glycoprotein are prime candidates for epitope-focused vaccine design. We report on a vaccine strategy that utilises a lipid core peptide (LCP) delivery system with self-adjuvanting properties in conjunction with either the antigenic site Ø or II (B cell epitopes) along with PADRE as a T helper cell epitope. These LCP constructs adopted the desired helical conformation in solution and were recognised by their cognate antibodies D25 and Motavizumab, specific for site Ø and II on RSV F protein, respectively. The LCP constructs were capable of eliciting higher levels of antigen specific antibodies than those induced by antigens administered with complete Freund's adjuvant, demonstrating the potent adjuvanting properties of LCP delivery. However, the antibodies induced failed to recognise native F protein or neutralise virus infectivity. These results provide a note of caution in assuming that peptide vaccines, successfully designed to structurally mimic minimal linear B cell epitopes, will necessarily elicit the desired immune response.