33rd Annual Scientific Meeting proceedings

Sarcoids are common skin tumors in horses induced by closely related bovine papillomavirus types 1 and 2 (BPV1, 2). To date, there are no universally effective sarcoid therapeutics so that tumors often recrudesce in a more severe, multiple form following treatment.

We generated NS1-deleted human influenza A and B viruses co-expressing shuffled BPV1 E6 and E7 peptides (iNSA-/iNSB-E6E7) as immunotherapeutic vaccines. We then demonstrated their safety and immunogenicity in an equine pseudo-sarcoid model. Subsequently, we conducted a clinical trial involving 29 horses with BPV1/2-induced mild (n=3), moderate (n=8), or severe (n= 18) sarcoid disease. Treatment consisted of repeated intratumoral injections with iNSA- and/or iNSB-E6E7. Then horses were closely monitoring with respect to adverse side effects and tumor sizes.

The vaccines proved safe and induced a strong systemic immune response. Application of iNSA- and/or iNSB-E6E7 into one to three selected sarcoids per horse led to complete eradication of injected and also non-injected lesions (complete remission; CR) in 14/29, and partial tumour regression (PR) in 4/29 equine patients. This result corresponds to an overall response rate of 62%. CR was achieved in 100% of mild, 50% of moderate, and 38.9% of severe cases, including 5/5 horses with therapy-resistant periocular sarcoids. Intriguingly, intratumoral injections with iNSA- and/or iNSB-E6E7 also resulted in clearance of BPV1 or BPV2 infection in 8/10 horses with CR.

Taken together, we have established a potent immunotherapeutic strategy for the treatment of sarcoids and, importantly, BPV infection underlying disease, thus minimizing the risk of disease recurrence.