Bovine papillomavirus is a worldwide distributed virus that affects at least 60% of Brazilian cattle herd, causing significant economic loses. Considering the great number of BPV-infected bovines, therapeutic vaccines, such those based on E6 protein, are mandatory to control the BPV-related diseases. However, the choice of the adjuvant remains challenging the vaccinology field, since adjuvants are associated with local and systemic reactions. Thus, this study analyzed the cytotoxic and mutagenic potential of BPV-1 E6 protein-based vaccine formulations using different adjuvants: aluminum hydroxide, complete and incomplete Freund’s adjuvants and two anti-oxidant saponinrich extracts obtained from Agave sisalana - alcoholic and acid hydrolysis extract. Results of these analyzes suggest that acid hydrolysis extract from A. sisalana is an alternative and useful candidate for therapeutic vaccines, being able to reduce the mutagenic potential of antigen.