An Ad26‐ <scp>MVA</scp> ‐ <scp>BN</scp> ‐based therapeutic vaccine targeting <scp>HPV16</scp> and <scp>HPV18</scp> related disease is immunogenic in preclinical models and in women with persistent <scp>HPV</scp> infections

Abstract Objectives To develop a therapeutic human papillomavirus (HPV) vaccine capable of intercepting HPV‐related cervical disease to reduce the number of new cancer cases and associated deaths. Methods We previously reported that replication‐deficient adenovirus type 26 and 35‐based vectors (Ad26, Ad35) expressing a fusion protein of E2, E6 and E7 (E2SH) from HPV16 and HPV18 induced robust HPV‐specific T‐cell immunity capable of reducing HPV16+ tumors in mice. Here, we assessed immune responses induced by Ad26 and Modified Vaccinia Virus Ankara—strain Bavarian Nordic (MVA‐BN) viral vectors expressing E2SH in heterologous vaccination regimens in mice, macaques and a limited number of persistently HPV‐infected women ( N = 5). Results The magnitude and breadth of cellular immune responses were higher in mice that received Ad26.HPV16/18‐MVA‐BN.HPV16/18 than in those that received Ad26.HPV16/18‐Ad35.HPV16/18, all expressing the fusion protein E2SH of HPV16 and HPV18. Sustained and broad antigen‐specific systemic T‐cell responses against HPV16 and HPV18 proteins were induced in macaques. In the Phase 1/2a trial, a 2‐dose heterologous immunisation with Ad26.HPV16 or Ad26.HPV18 in Week 0 and MVA‐BN.HPV16/18 in Week 8 induced long‐lived antigen‐specific cytokine‐producing T cells. After Week 8, HPV16/18 infection was no longer detected in 5/5 active vaccines and 1/4 placebo recipients during the study period of approximately 1 year. The small number of vaccinated participants did not allow concluding on the relationship between immune responses and viral clearance. Conclusion These data show the ability of Ad26.HPV16/18‐MVA‐BN.HPV16/18 heterologous regimens to elicit HPV‐specific T‐cell responses and warrant further clinical studies to evaluate vaccine efficacy.