Role of regulatory T-cells in immunization strategies involving a recombinant alphavirus vector system.

Background: Regulatory T-cells (Treg) hamper immune responses elicited by cancer vaccines. Therefore, depletion of Treg is being used to improve the outcome of vaccinations. Methods: We studied whether an alphavirus vector-based immunotherapeutic vaccine changes the number and/or activity of Treg and if Treg depletion improves the efficacy of this vaccine against tumours. The vaccine is based on a Semliki Forest virus (SFV). The recombinant SFV replicon particles encode a fusion protein of E6 and E7 from human papillomavirus (HPV) type 16 (SFVeE6,7). Results: We demonstrated that SFVeE6,7 immunization did not change Treg levels and their suppressive activity. Depletion of Treg in mice, using the novel anti-folate receptor 4 antibody, did not enhance the immune response induced by SFVeE6,7 immunization. Both the priming and the proliferation phases of the HPV-specific response elicited with SFVeE6,7 were not affected by the immune-suppressive activity of Treg. Moreover, Treg depletion did not improve the therapeutic antitumour response of SFVeE6,7 in a murine tumour model. Conclusions: The efficacy of the SFVeE6,7 vaccine was not hampered by Treg. Therefore, SFVeE6,7 seems a very promising candidate for the treatment of HPV-induced disease, as it may not require additional immune interventions to modulate Treg activity.