Sabine Brandt (Austria)
University of Veterinary Medicine Small Animals and HorsesPresenter of 1 Presentation
RECOMBINANT LIVE-ATTENUATED INFLUENZA VIRUSES CO-EXPRESSING BOVINE PAPILLOMAVIRUS 1 (BPV1) E6 AND E7 INDUCE TUMOUR REGRESSION IN EQUINE SARCOID PATIENTS (ID 768)
Abstract
Introduction
Bovine papillomaviruses types 1 and 2 (BPV1, BPV2) induce semi-malignant skin tumours termed sarcoids in horses. Sarcoids seriously compromise the health and welfare of affected individuals due to their high propensity to progress upon accidental or iatrogenic trauma, and to reoccur in a more severe, multiple form following ineffective treatment.
Methods
We have developed live-attenuated influenza (Flu) A and B viruses co-expressing shuffled BPV1 E6 and E7 antigens as potential sarcoid immunotherapeutic.
Results
In a phase I trial involving 12 sarcoid- and BPV1/2-free horses, intradermal administration of vaccine candidates was well tolerated with the only transient side effect being mild fever in four horses for < 8 hours following first administration of the Flu A BPV1-E6E7 virus. Importantly, vaccine candidates also proved biologically safe: repeated screening of secretions and faeces by RT-PCR and focus forming assay in the course of the trial demonstrated the absence of virus shedding.
In an ongoing patient trial involving 30 horses bearing multiple, partly recurrent sarcoids, one lesion per horse was injected three times (days 1, 3, 5) with the influenza A virus, and then boosted three times with the influenza B virus (days 8, 10 and 12). Treatment led to significant tumour regression in five, and stable disease in three patients subjected to this therapeutic regimen thus far. In two patients, tumours recurred 5 months post treatment, indicating that the viral vaccines and/or treatment schedule need to be further optimized as to induce a long-lasting therapeutic effect in all the patients. Immunotherapy is currently repeated in these horses.
Intriguingly, treatment also had a systemic effect in all individuals as revealed by synchronous regression or growth arrest of non-injected lesions located at different sites of the horses’ integument
Conclusions
To our knowledge, this is the first immunotherapeutic approach showing significant reduction of tumour burden in equine sarcoid patients.