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PloS one2021; 16(11); e0260155; doi: 10.1371/journal.pone.0260155

Influenza virus vector iNS1 expressing bovine papillomavirus 1 (BPV1) antigens efficiently induces tumour regression in equine sarcoid patients.

Abstract: Bovine papillomaviruses types 1 and 2 (BPV1, BPV2) commonly induce skin tumours termed sarcoids in horses and other equids. Sarcoids seriously compromise the health and welfare of affected individuals due to their propensity to resist treatment and reoccur in a more severe form. We have developed influenza (Flu) A and B virus vectors that harbour a truncated NS1 gene (iNS) assuring interferon induction and co-express shuffled BPV1 E6 and E7 antigens for sarcoid immunotherapy. In a safety trial involving 12 healthy horses, intradermal administration of 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 by RT-PCR and plaque assay revealed no virus shedding, thus also confirming biological safety. In a patient trial involving 29 horses bearing BPV1-induced single or multiple sarcoids, at least one lesion per horse was intratumourally injected and then boosted with iNSA/E6E7equ and/or iNSB/E6E7equ. The treatment induced a systemic antitumour response as reflected by the synchronous regression of injected and non-injected lesions. Irrespective of vaccination schemes, complete tumour regression was achieved in 10/29 horses. In 10/29 horses, regression is still ongoing (May 2021). Intriguingly, scrapings collected from former tumour sites in two patients tested negative by BPV1 PCR. Nine severely affected individuals with a history of unsuccessful therapeutic attempts did not (6/29) or only transiently (3/29) respond to the treatment. INSA/E6E7equ and iNSB/E6E7equ proved safe and effective in significantly reducing the tumour burden even in severe cases.
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Publication Date: 2021-11-19 PubMed ID: 34797850PubMed Central: PMC8604313DOI: 10.1371/journal.pone.0260155Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The researchers developed a treatment for skin tumors in horses caused by bovine papillomaviruses types 1 and 2, using innovative influenza virus vectors that co-express certain bovine papillomavirus antigens. The treatment was well tolerated in a safety trial, did not cause virus shedding, and in a patient trial it induced a system-wide anti-tumor response, with complete tumor regression in a third of the horses.

Pathology of Bovine Papillomaviruses

  • Bovine papillomaviruses types 1 and 2 (BPV1, BPV2) are known to cause skin tumors, or sarcoids, in horses and other equids.
  • These tumors are a significant health concern due to their resistance to treatment and tendency to reoccur in a more severe form.

Development of New Treatment

  • The study involved developing influenza A and B virus vectors that contain a truncated NS1 gene (iNS) which ensures the induction of interferon, an important substance in the immune response against viral infections.
  • The virus vectors also co-express shuffled versions of BPV1 E6 and E7 antigens, aimed at triggering an immune response against the tumor cells.

Safety Trial Results

  • A safety trial involved 12 healthy horses being treated with these influenza virus vectors.
  • The treatment was well tolerated, with the only side effect being a mild fever in four of the horses. This side effect was temporary.
  • No virus shedding was detected in the horses’ secretions and faeces, demonstrating the biological safety of the treatment.

Patient Trial Results

  • The patient trial involved 29 horses with BPV1-induced sarcoids.
  • Each horse had at least one lesion injected with the treatment, and a boost given of either iNSA/E6E7equ and/or iNSB/E6E7equ.
  • The treatment created a system-wide anti-tumor response, as shown by the simultaneous regression of both treated and non-treated lesions.
  • Irrespectively of the vaccination schemes, complete tumor regression was achieved in 10 out of 29 horses, and regression was still ongoing in another 10 horses as of May 2021.
  • No BPV1 was detected in scrapings from former tumor sites of two patients, indicating the effectiveness of the treatment.

Summary

  • However, nine horses with a history of unsuccessful therapeutic tries did not respond or only transiently responded to the treatment. This suggests its effectiveness could be compromised in more severe or complex cases.
  • Nevertheless, the treatment proved to be safe and effective in mostly reducing the tumor burden even in severe instances. A third of the horses experienced complete tumor regression, and another third were still experiencing tumor regression.

Cite This Article

APA
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

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 16
Issue: 11
Pages: e0260155
PII: e0260155

Researcher Affiliations

Jindra, Christoph
  • Department of Companion Animals and Horses, Division of Equine Surgery, Research Group Oncology, University of Veterinary Medicine, Vienna, Austria.
Hainisch, Edmund K
  • Department of Companion Animals and Horses, Division of Equine Surgery, Research Group Oncology, University of Veterinary Medicine, Vienna, Austria.
Rümmele, Andrea
  • Department of Companion Animals and Horses, Division of Equine Surgery, Research Group Oncology, University of Veterinary Medicine, Vienna, Austria.
Wolschek, Markus
  • BlueSky Immunotherapies, Vienna, Austria.
Muster, Thomas
  • BlueSky Immunotherapies, Vienna, Austria.
Brandt, Sabine
  • Department of Companion Animals and Horses, Division of Equine Surgery, Research Group Oncology, University of Veterinary Medicine, Vienna, Austria.

MeSH Terms

  • Animals
  • Bovine papillomavirus 1 / immunology
  • Chlorocebus aethiops
  • Disease Vectors
  • Female
  • Horses
  • Humans
  • Influenza, Human / immunology
  • Male
  • Neoplasms / immunology
  • Neoplasms / virology
  • Orthomyxoviridae / immunology
  • Sarcoidosis / pathology
  • Sarcoidosis / virology
  • Vaccination / methods
  • Vero Cells
  • Virus Shedding / immunology

Conflict of Interest Statement

All authors declare that they have no competing interests.

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Citations

This article has been cited 5 times.
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