Kelly, J. T.; Dellosa, G. K.; Newman, J.; Hills, R.; Mohamed, A. A. M.; Aniscenko, J.; Johnston, S. L.; Tuthill, T. J.

Infection with rhinovirus (RV) is associated with significant morbidity and hospitalisation in people with chronic lung disease. At present there is no approved RV vaccine or antiviral. There are approximately 180 RV serotypes, classified into 3 species (RVA, RVB, RVC). There is no cross-protection between serotypes because of high diversity in immunodominant antigenic sites. This makes it impractical to create a broadly protective vaccine using traditional methods, involving whole capsids. A more feasible strategy is to direct the immune response towards conserved but less dominant epitopes. The capsid protein VP4 is highly conserved within each RV genotype and some antibodies that target VP4 are neutralising. This makes VP4 vulnerable to antibodies and a promising vaccine target. Here we investigate the ability of RV VP4 N-terminal peptides presented on different display systems to initiate a neutralising immune response in mice. We compared three different-sized VP4 peptides (spanning residues, 1-15, 1-30 and 1-45) displayed on two different display systems- SpyCatcher Virus-like particles (VLPs) or Keyhole Limpet Hemocyanin (KLH). Overlapping regions of VP4 were antigenically different when presented on different platforms and in peptides with different length. The conformation of the 1-15 region of VP4 was critical for inducing antibodies that were both neutralising and able to bind VP4 in the context of the virus particle. Therefore, correctly displayed VP4 peptides can recapitulate virus-like antigenicity. These findings improve our understanding of VP4 antigenicity and will inform the design of future RV vaccines. This work could also impact the design of other peptide vaccines, since a variable antigenic conformation is a common characteristic of pathogen-derived peptide targets.