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Cross-Serotype Immunity Induced by Immunization with a Conserved Rhinovirus Capsid Protein
Authors:Nicholas Glanville  Gary R Mclean  Bruno Guy  Valerie Lecouturier  Catherine Berry  Yves Girerd  Christophe Gregoire  Ross P Walton  Rebecca M Pearson  Tatiana Kebadze  Nicolas Burdin  Nathan W Bartlett  Jeffrey W Almond  Sebastian L Johnston
Institution:1. Airways Disease Infection Section, National Heart and Lung Institute, Medical Research Council and Asthma United Kingdom Centre in Allergic Mechanisms of Asthma, Centre for Respiratory Infections, Imperial College London, London, United Kingdom.; 2. Discovery Department, Sanofi Pasteur, Campus Merieux, Marcy l''Etoile, France.; Nationwide children''s Hospital and Ohio State University, United States of America,
Abstract:Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine.
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