Genetically altered flu virus successfully knocked back sarcoids in horses

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An injection with iNSA/E6E7equ on d0, d28, d86 led to tumour regression and no bovine papillomavirus type 1 DNA was detectable anymore from the tumour site. The pictures chart progress before treatment, then after 5 months, 7 months and 10 months. Images: Jindra et al. <a href="https://doi.org/10.1371/journal.pone.0260155.g006" target="_blank" rel="noopener"><span style="text-decoration: underline;">https://doi.org/10.1371/journal.pone.0260155.g006</span></a>
An injection with iNSA/E6E7equ on d0, d28, d86 led to tumour regression and no bovine papillomavirus type 1 DNA was detectable anymore from the tumour site. The pictures chart progress before treatment, then after 5 months, 7 months and 10 months. Images: Jindra et al. https://doi.org/10.1371/journal.pone.0260155.g006

A treatment using the influenza virus as a vector for an altered gene shows promise as a treatment for sarcoids in horses, researchers in Austria report.

Sarcoids in horses are linked to the presence of bovine papillomaviruses types 1 and 2 (BPV1 and BPV2). These locally aggressive skin tumours can seriously compromise the health and welfare of affected animals.

State-of-the-art treatments include surgical excision, ligature use, cryotherapy, chemotherapy, or combinations of these. However, in a substantial number of cases, treatment leads to tumour recurrence, usually in a more aggressive form.

There is a strong need for more effective sarcoid therapeutics because of their propensity to resist treatment and reoccur in a more severe form.

Christoph Jindra, Edmund Hainisch and their fellow researchers developed influenza A and B virus vectors for sarcoid immunotherapy that harbour a truncated NS1 gene, assuring interferon induction, and co-expressing shuffled BPV1 E6 and E7 antigens.

The alterations mean the virus cannot give horses the flu, but it retains the ability to replicate efficiently in tumour cells sensitive to interferon.

In a safety trial involving 12 healthy horses, administration of the two agents they developed, dubbed iNSA/E6E7equ and iNSB/E6E7equ, was well tolerated, with the only transient side-effect being mild fever in four horses.

Repeated screening of secretions and faeces revealed no virus shedding, the study team reported in the open-access journal PLOS ONE.

In a patient trial involving 29 horses with BPV1-induced single or multiple sarcoids, at least one lesion per horse was injected and then boosted with iNSA/E6E7equ and/or iNSB/E6E7equ.

Complete tumour regression was achieved in 10 of the 29 horses. In 10 horses, regression was still ongoing as of May this year, meaning that regression was achieved in 20 of the 29 equine patients.

“Intriguingly,” they reported, “regression was not restricted to injected sarcoids but also observed for non-injected lesions, which is consistent with a systemic and sarcoid-specific immune response.”

In most cases, both injection schedules used in the study (into the tumours on days 0, 2, 4, 7, 9 and 11, or on days 0, 28 and 86) led to satisfactory results.

“Given that the first schedule requires permanent stabling of horses at a Biosafety Level 2 facility for more than two weeks, whereas the second schedule only necessitates three stays overnight, the latter has been adopted as standard procedure for welfare reasons.”

Intriguingly, scrapings collected from former tumour sites in two patients were negative for BPV1, based on the results of molecular-based testing.

Six severely affected individuals with a history of unsuccessful therapeutic attempts did not respond to the treatment, and another three responded only transiently.

The authors described their findings as very encouraging, with further refinements likely after considering fresh immunological data.

They said INSA/E6E7equ and iNSB/E6E7equ proved safe and effective.

The technique proved effective in reducing or eliminating the sarcoid burden, even in severe cases, and showed the ability to clear the BPV1/2 infection that underlies disease development.

The study team comprised Jindra, Hainisch, Andrea Rümmele and Sabine Brandt, all with the oncology research group at the University of Veterinary Medicine in Vienna, Austria; and Markus Wolschek and Thomas Muster, both with BlueSky Immunotherapies, also in Vienna.

Jindra C, Hainisch EK, Rümmele A, Wolschek M, Muster T, Brandt S (2021) Influenza virus vector iNS1 expressing bovine papillomavirus 1 (BPV1) antigens efficiently induces tumour regression in equine sarcoid patients. PLoS ONE 16(11): e0260155. https://doi.org/10.1371/journal.pone.0260155

The study, published under a Creative Commons License, can be read here

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