Pre-clinical development of a novel cross-protective rhinovirus vaccine.

<bold>Background:</bold> Rhinovirus (RV) infection is the major cause of the common cold and represents a significant worldwide healthcare burden. RVs primarily cause mild self-limiting infections, but in infants and patients with chronic lung diseases they can drive severe respiratory illness and are responsible for most acute asthma and COPD exacerbations. Development of an effective RV vaccine has proved challenging due to the antigenic heterogeneity amongst the ~180 strains. <bold>Aim:</bold> To assess the immunogenicity and efficacy of a novel RV VP0 vaccine, particularly its capacity to induce protective immunity against heterotypic RV strains. <bold>Methods:</bold> Mice or non-human primates (NHPs) received prime and boost immunisations of an adjuvanted single strain RV VP0 vaccine. Four weeks post boost immunisation, mice were infected with live heterotypic RV-A01. Cellular and humoral immune responses were analysed. <bold>Results:</bold> Immunisation with a RV VP0 vaccine candidate produced high and sustained concentrations of vaccine-specific serum IgG in mice and NHPs and enhanced type 1 responses to RV VP0 peptide pools from up to 19 heterotypic RV-A, -B and -C strains. In RV-A01 infected mice, vaccination enhanced T and B lymphocyte activation and maturation, promoting development of long-lived tissue-resident memory cells in the respiratory tract, boosting heterotypic neutralising antibody titres, and accelerating virus clearance. <bold>Conclusions:</bold> In mice and NHPs, this RV VP0 vaccine has shown strong immunogenicity and enhanced anti-viral immunity against multiple heterotypic RV strains. This vaccine candidate will enter phase 1 trials in the near future.