THE BIOMEDICAL RESEARCH CENTRE SEMINAR SERIES
“Towards a Vaccine for Human Rhinoviruses” by
Dr. Gary McLean
Honorary Research Fellow – Imperial College London
Reader in Molecular Immunology – London Metropolitan University
Monday March 9, 2015
4:00pm to 5:00pm
The Biomedical Research Centre
2222 Health Sciences Mall
Host: Dr. Hermann Ziltener (Hermann@brc.ubc.ca)
Abstract: Human rhinovirus (RV) infections are the principle cause of common colds and are an important viral trigger responsible for exacerbations of asthma and chronic obstructive pulmonary disease. Currently there is no vaccine for RV, a consequence of the existence of ~150 serotypes/strains and little or no cross-protective immunity generated from natural infections. Highly conserved regions of the RV polyprotein, when used as an immunogen with an appropriate adjuvant, are hypothesized to generate broadly cross-reactive protective immunity to RV. A bioinformatic approach to define highly conserved areas of the RV proteome was performed. Recombinant proteins covering these areas were produced and tested for usefulness as candidate immunogen for a broadly cross-reactive vaccine using a mouse RV infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having the highest homology across RVs. Immunization with recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after challenge with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies, specific T cells and caused more rapid virus clearance.
In conclusion, conserved domains of the RV capsid are immunogenic in mice, inducing cross-reactive immune responses that neutralise RV in vitro and are protective in vivo when combined with a Th1 promoting adjuvant. This approach has identified a candidate for the continued development of a broadly reactive subunit RV vaccine.