Background

Rhinoviruses (RV) are highly prevalent respiratory pathogens responsible for the majority of common colds in healthy persons. In patients with chronic lung conditions, RV infection can exacerbate disease and cause severe lower respiratory tract inflammation. The large antigenic variety across the ~180 known RV strains has so far thwarted development of an effective vaccine.

Aim

To investigate the immune response to an RV-A16 VP0 mRNA vaccine and subsequent RV-A01 infection.

Methods

Mice were immunised with RV-A16 VP0 mRNA using a standard prime and boost protocol. Four weeks post boost, mice were infected with live RV-A01.  

Results

Immunisation with RV-A16 VP0 mRNA induced high and sustained concentrations of RV-A16 VP0-specific serum IgG and produced tissue resident memory (T_RM) IFN-?⁺ CD4 T cells which responded to heterotypic RV-A peptides. Vaccination accelerated clearance of RV-A01 infection and was associated with increased neutrophil and lymphocyte recruitment to the airways, and earlier anti-viral T cell responses in the lungs and airways. Mature lung T cell phenotypes including T_RM and antigen-specific T cells were prominent in vaccinated mice compared to unvaccinated mice. Further, splenocytes from vaccinated mice showed enhanced cross-reactivity to peptide pools from 7 heterotypic RV-A strains and one RV-B strain: a response further boosted by RV-A01 infection.

Conclusions

Immunisation with RV-A16 VP0 mRNA generates cross-strain RV-responsive T cell populations which are primed to respond faster and more effectively to heterotypic RV infection, accelerating lung virus clearance.