Intranasal boosting enhances genital tract T cell immunity following ChAdOx1/MVA hrHPV therapeutic vaccination

High risk human papillomaviruses (hrHPV) infect mucosal epithelia and are the causative agents of cervical cancer. Prophylactic vaccines protect against disease caused by several, but not all hrHPV types. Furthermore, prophylactic vaccines are not widely available to populations with the greatest disease burden and have no therapeutic effect in previously infected individuals. Therapeutic vaccines that enhance host immunity in individuals with persistent hrHPV infections represents a promising strategy to support cervical cancer control. However, efficacy of a therapeutic vaccine depends not only on antigen selection and delivery system, but also on the route of immunisation. Because cervical intraepithelial lesions are confined to the genital mucosa, an effective therapeutic vaccine may need to elicit immune effector cells at the site of disease. Here we study the effect of immunisation route on vaccine immunogenicity using previously described ChAdOx1- and MVA-vectored hrHPV therapeutic vaccines encoding a multigenotype insert. In addition, we used GFP-expressing viral-vectored vaccines to monitor vaccine uptake in the cervix by real-time in vivo imaging. Among all regimens tested, the intramuscular prime-intranasal boost induced the highest magnitude of E6-specific CD8⁺ T cells in both the spleen and cervicovaginal compartment, and also generated the greatest frequency of cervicovaginal CD8⁺ T_RM cells.