An Ad26-MVA-BN-based therapeutic vaccine targeting HPV16 and HPV18 related disease is immunogenic in preclinical models and in women with persistent HPV infections.

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.