Introduction

Clearance of HPV and related cervical lesions is associated with the development of a robust T cell response. Therapeutic vaccination is a promising approach to restore T cell immunity, treat infections and malignancies. A two-dose heterologous vaccination strategy using non-replicating viral vectors, Chimpanzee Adenovirus Oxford 1 (ChAdOx1) and Modified Vaccinia virus Ankara (MVA), has been safe and immunogenic in clinical studies across various indications. This is the first study to evaluate the safety, tolerability, immunogenicity and efficacy of ChAdOx1 and MVA in participants with persistent cervical high-risk HPV (hrHPV) infection and low-grade cervical lesions.

Methods

MVA boosts and prolongs the T cells induced by ChAdOx1. Doses of ChAdOx1 up to 5 x 10¹⁰ vp and MVA doses up to 2.5 x 10⁸ pfu have been evaluated in various indications. We will investigate different doses of ChAdOx1 and MVA to deliver sequences from high risk HPV strains (16, 18, 31, 52, 53 and 58). The study will be conducted sequentially under an umbrella protocol design (Fig 1):

- An open label dose escalation study investigating 3 varying doses of ChAdOx1 (baseline) and a fixed dose of MVA (Day 28) with a 3-months follow-up period (n=9).

- A blinded, randomised (2:1), placebo-controlled study investigating 3 varying doses of ChAdOx1 (baseline) and 2 doses of MVA (Day 28) with a 12-month follow-up period (n=96).

Results

105 participants will be enrolled. The primary objective is to evaluate safety of both vaccines. The secondary objectives will include dose determination for further development, clearance of hrHPV infection and resolution of associated cervical lesions.

Conclusions

The success of therapeutic vaccination depends on an appropriate prime-boost vaccination strategy. This study evaluates the impact of a heterologous prime boost therapeutic vaccination strategy to clear persistent cervical hrHPV infection and revert low-grade cervical lesions. Available study results will be presented at the meeting.