A rhinovirus vaccine evokes T cell mediated cross-reactive immunity in a preclinical model of rhinovirus infection

Abstract

Rhinovirus (RV) infection is the most common cause of acute exacerbations of respiratory diseases such as asthma and chronic obstructive pulmonary disease. Vaccines are available for two less common respiratory viruses (influenza and respiratory syncytial viruses), but development of a RV vaccine to protect patients with chronic respiratory disease has been hampered by the large number of serologically distinct RV strains ([~]180, grouped genetically into [~]80 A, [~]30 B and [~]70 C strains). We have explored the potential of the RV-A16 VP0 subunit vaccine in both CpG-adjuvanted protein subunit and mRNA formats. We demonstrate that both vaccine formats induce strong effector CD4 and CD8 T cell responses in the airways and lungs of immunized mice that rapidly expand following infection with a heterotypic RV strain and are associated with enhanced virus clearance. Adjuvanted VP0 protein subunit vaccination evoked strong germinal center reactions in the lymph nodes and markedly accelerated the production of neutralizing antibodies following heterotypic RV infection. In contrast, VP0 mRNA vaccination evoked limited germinal center responses and neutralizing antibody production. Th1 polarized immune responses were induced against a large panel of 20 heterologous RV strains representative of all RV-A, -B and -C strains. This study confirms the potential of RV VP0 vaccination as an approach to overcome the serological diversity of RV and describes the immune response evoked, including cross-strain cellular immunity and protection against heterotypic RV infection.