Virbagen Omega

					VIRBAGEN® OMEGA: THE POTENTIAL OF A
VETERINARY INTERFERON
Dr. Claudia Vischer BVSc (Hons)
Technical Services Manager
Virbac (Australia) Pty Limited


Introduction:

Virbagen®Omega is the first veterinary interferon to be registered in Australia.
It is a recombinant omega interferon of feline origin (rFeIFN- ω) produced by
genetic engineering. Virbagen®Omega is a Type 1 Interferon, closely related
to the human alpha and beta interferons. Like all interferons it has antiviral,
immunomodulatory and antiproliferative properties.

Interferons are protein molecules which are secreted temporarily by almost all
cell types in response to invasion by a virus, bacteria or tumour cells and play
a major role in the host’s defence mechanisms. They belong to the cytokine
family (like interleukins). The interferon family can be subdivided into two
subtypes on the basis of physiochemical and biological properties.

Type 1 Interferons: IFN-α, IFN-β, IFN-ω
Type 2 Interferons: IFN-γ

Human interferons have an important role in the treatment of specific
diseases in human medicine, such as hepatitis B and C, papilloma virus,
certain forms of leukaemia, haemangioma and multiple sclerosis.


Mode of action:

Interferons bind to specific receptors on the plasma membrane of other cells.
There is one receptor for Type 1 Interferons (α, β, and ω) and another one for
the only Type 2 Interferon (IFN-γ). The binding activates a complex
transcriptional cascade, leading to the up-regulation of greater than 20 cellular
genes, producing an interferon-activated cell. IFN-induced proteins are
numerous and each protein confers a new property to the cell. This may be
antiviral, immune modulating or antiproliferative.

The antiviral effect of an interferon-activated cell results from the induction of
specific proteins which inhibit viral multiplication and viral protein synthesis.
When a virus infects an interferon-activated cell, the immune response is also
modulated with up-regulation of the cell-mediated immune system.
Leucocytes are stimulated and there is an increase in cytotoxic activity,
natural killer cell activity and oxidase activity by neutrophils. There is an
increase in antigen presentation by the cell and an increase in apoptosis
receptors in the cell membrane. All of these processes induce an “antiviral
state” and result in death of virus infected cells.
The antiproliferative effect of an interferon-activated cell results from the
induction of a specific protein which activates gene enhancers and gene
silencers. The gene silencer inhibits the expression of the oncogene and the
gene enhancer activates the tumour suppressor gene. Hence there is
regulation of the genes controlling cell division leading to the inhibition of cell
proliferation and an antitumoral effect.

In contrast to antibodies, interferons are secreted transiently in response to
virus infections. They are induced by almost any virus, multiplying in almost
any cell type, and in any vertebrate species. However, they are mostly host
specific. For example, mouse interferons are ineffective in humans and vice
versa. Recombinant human interferons have been used in veterinary
medicine, however the development of antibodies is thought to be one
mechanism which renders the product ineffective. In-vitro trials using a
canine cell model and field trials, which assessed the efficacy of the rFeIFN in
dogs, have proven that the omega interferon, although of feline origin, exerts
significant cross-species effects when administered to dogs. This may be due
to the evolutionary relatedness of carnivores. On the other hand, interferons
are not virus specific. Interferons induced during a distemper infection are
effective against a parvovirus infection, locally and/or after distribution
throughout the body.


Manufacture of Virbagen®Omega:

The rFeIFN-ω molecule is produced by genetic engineering using an original
technology that results in a defined, pure and safe product. Live silkworms
(Bombyx mori) are inoculated with a recombinant baculovirus vector that
carries the feline IFN-ω gene sequence. This feline IFN-ω gene sequence is
translated into the feline interferon protein in the insect larvae.

Multiple laboratory and field studies have demonstrated that the safety of the
interferon preparation is excellent in both dogs and cats. Due to the safety
aspect and universal antiviral activity of interferons, Virbagen ®Omega
presents a wide range of applications in veterinary medicine and should
become a state-of-the-art drug, as it has in human medicine.


Indications of Virbagen®Omega:

Virbagen®Omega is currently registered in Australia as an adjunct in the
treatment of canine parvovirus and feline calicivirus infections.              In
                                                  ®
laboratory and field trials the use of Virbagen Omega has shown to reduce
the mortality rate, clinical signs and lesions associated with canine parvovirus,
and reduce the duration and severity of fever and oral ulceration associated
with feline calicivirus.

The current registered dose rates in Australia are:
Dogs -       2.5 MU/kg IV SID for 3 consecutive days.
Cats -       5 MU/kg IV SID every other day for 3 injections.

The large potential of Virbagen®Omega due to its properties, represents very
promising new treatment options in the management of viral diseases in cats
and dogs with immunotherapy.

Clinical studies have demonstrated its benefits when used in FIV and/or FeLV
infected symptomatic cats, and has been approved for this indication in
Europe. Other areas of interest with supporting and ongoing clinical studies
and reports include FIP, herpetic keratitis, feline chronic gingivostomatitis
and distemper. Relevant publications for each of these conditions are listed
below in the references.

Due to the antiviral and immunomodulatory properties of Virbagen®Omega it
represents the possibility of a new therapeutic modality in the treatment of
feline chronic gingivostomatitis (FCGS). The use of Virbagen®Omega in
FCGS has been evaluated and assessed under clinical conditions by an
independent practitioner in Germany, Susann-Y. Mihaljevic. The results of
this study were presented at the B.P.T. Congress (German Association of
Practicing Veterinarians) in November 2002 and published in a German
Journal in 2003 (Der Praktische Tierarzt 2003; 84:5, 350 – 361).

In this clinical study (Mihaljevic S.-Y.,2003) 20 cats presenting with moderate
to severe chronic gingivitis, stomatitis and/or oropharyngitis (GSO) were
administered rFeIFN subgingivally and subcutaneously, either as sole therapy
or in combination with other individual therapeutic measures (dental
treatment, antibiotics, para-immunisation with nonspecific immunomodulators,
“home care” ie. local use of chlorhexidine, aloe, special diets, stress-free
environment). The results of the treatment were recorded for at least three to
six months.

It was concluded that along with thorough dental treatment, which should be
followed up with oral control radiographs where possible, rFeIFN- ω, either
alone or as part of combination therapy, represents a very promising new
treatment option for chronic GSO in the cat. Following the overwhelmingly
positive results with the feline omega interferon, a new treatment protocol for
chronic GSO is suggested (refer to Mihaljevic S.-Y.,2003 for further details).

For further details on suggested treatment regimes refer to the published
papers listed below or contact Virbac.

Data for all these potential uses and new opportunities for Virbagen ®Omega
are continually being generated through on-going studies to improve the
management of these cases, evaluate the benefits of interferon therapy and
determine the optimal treatment regimes.
REFERENCES:

Parvovirus Infection:

De Mari K., Maynard L., Eun H.M., Lebreux B. (2003) – Treatment of canine parvoviral enteritis with interferon-omega
in a placebo-controlled field trial. Vet. Rec., 152: 105 – 108

Martin V., Najbar W., Gueguen S., Grousson D., Eun H.M., Lebreux B. Aubert A. (2002) – Treatment of canine
parvoviral enteritis with interferon-omega in a placebo-controlled challenge trial. Vet. Microbiol.; 89 : 115 – 127

Minagawa T., Ishiwata K., Kajimoto T. (1999) - Feline interferon-omega treatment on canine parvovirus infection. Vet.
Microbiol.; 69 : 51 – 53

Le Foll C. (2003) – A cat suffering from panleucopenia. L´Action Vétérinaire 12/03, No. 1659: 7 - 9

Addie D., Buonavoglia C., Camy G., McCann T., Gunn-Moore D., Hartmann K., Hennet P., Ishida T., Jongh O.,
Lanore D., De Mari K., Mihaljevic S-Y., Péchereau D., Régnier A., Thiry E., Vinet C. (2004) – Veterinary Interferon
Handbook. First Edition


Calici virus (cat flu) :

Gaskell R., Dawson S. (1998) – Feline respiratory disease in infectious diseases of the dog and cat, Greene – WB
Sanders Company; 2nd edition: 97 – 106

Uchino T., Yamane Y., Motoyoshi S. (1992) – Study of clinical efficacy and safety of KT-80 on feline calicivirus
infection in field trial. Final trial report.

Uchino T. et al. (1992) – Investigations of feline interferon and its therapeutic effects for field use. Its therapeutic
effects on feline calicivirus infection. Shodobutsu Rinshou, Journal of Small Animal Clinical Science.

Uchino T. et al. (1999) – A large-scale field study of feline interferon on feline calicivirus infection. Trial report.

Addie D., Buonavoglia C., Camy G., McCann T., Gunn-Moore D., Hartmann K., Hennet P., Ishida T., Jongh O.,
Lanore D., De Mari K., Mihaljevic S-Y., Péchereau D., Régnier A., Thiry E., Vinet C. (2004) – Veterinary Interferon
Handbook. First Edition


FeLV / FIV:

De Mari K., Maynard L., Lebreux B. (2002) – Effects of a feline recombinant interferon on the survival and clinical
signs of ill FeLV- and/ or FIV-infected cats. In Proceedings of the 6th International Feline Retrovirus Research
Symposium, Amelia Island, Florida, USA, December 2002: 52

De Mari K. et al. (2004) – Therapeutic effects of recombinant feline interferon-omega on FeLV-infected and
FeLV/FIV-coinfected symptomatic cats. J.Vet.Intern.Med. July 2004

De Mari K. et Sanquer A. - Effects of a recombinant feline omega interferon on a population of FeLV and/or FIV
infected cats suffering from anaemia. In Proceedings of the 7th International Feline Retrovirus Research Symposium,
Pisa, Italy, September 2004: 74

Addie D.D. et al. (2000) – Long-term impact on a closed household of pet cats of natural infection with feline
coronavirus, feline leukaemia virus and feline immunodeficiency virus; Vet. Rec., 146 : 419 - 424

Greene C.E. (1998) – Clinical microbiology and infectious diseases of the dog and the cat; 2 nd edition, WB Saunders
Company: 71 - 96

Addie D., Buonavoglia C., Camy G., McCann T., Gunn-Moore D., Hartmann K., Hennet P., Ishida T., Jongh O.,
Lanore D., De Mari K., Mihaljevic S-Y., Péchereau D., Régnier A., Thiry E., Vinet C. (2004) – Veterinary Interferon
Handbook. First Edition


FIP:

Fradin-Ferme M. et al. (1999) – La Péritonite Infectieuse Féline ; Prat. Med. Chir. Anim. Comp., 34 : 309 – 319

Ishida T. et al. (2002) – Recombinant feline interferon therapy of feline infectious peritonitis; Proceedings of the 2 nd
International FCoV/ FIP Symposium, Glasgow, UK, August 2002: 17

Rohrer C. et al. (1993) – Die Diagnostik der felinen infektiösen Peritonitis (FIP): retrospektive und prospektive
Untersuchungen. Kleintierpraxis 6: 379 - 381
Addie D., Buonavoglia C., Camy G., McCann T., Gunn-Moore D., Hartmann K., Hennet P., Ishida T., Jongh O.,
Lanore D., De Mari K., Mihaljevic S-Y., Péchereau D., Régnier A., Thiry E., Vinet C. (2004) – Veterinary Interferon
Handbook. First Edition


Feline Herpes keratitis/conjunctivitis:

Verneuil M. (2004) – Topical application of feline interferon omega in the treatment of herpetic keratitis in the cat:
Preliminary study. Proceedings of ECVO, June 2004, München, Deutschland

Richter M. et al. (2003) – Activity of topically and orally applied interferon omega in cats by Mx protein expression in
conjunctival and white blood cells. Proceedings of ACVO, October 2003, Idaho, USA

Schmidt-Morand D., Jongh O. (2003) – Kératite Herpétique chez le chat: conduite thérapeutique et résultats.
Proceedings of AFVAC congress, November 2003, Nantes, France

Siebeck N. et al. (2004) – Inhibitory effects of recombinant feline omega interferon on the replication of feline
herpesvirus 1 in vitro. Proceedings of ECVO, June 2004, Munich, Germany

Truyen U. et al. (2002) A study of the antiviral activity of Interferon omega against selected canine and feline viruses.
Der Praktische Tierarzt 2002; 10: 862 - 865

Addie D., Buonavoglia C., Camy G., McCann T., Gunn-Moore D., Hartmann K., Hennet P., Ishida T., Jongh O.,
Lanore D., De Mari K., Mihaljevic S-Y., Péchereau D., Régnier A., Thiry E., Vinet C. (2004) – Veterinary Interferon
Handbook. First Edition


Feline Chronic Gingivo-Stomatitis (FCGS):

Mihaljevic S.-Y. (2003) – First clinical experiences with omega-interferon in the treatment of chronic gingivitis-
stomatitis-oropharyngitis of cats. Der Praktische Tierarzt 2003; 84:5, 350 - 361

Cami G. (2003) – A clinical case of chronic feline gingivitis-stomatitis. Special Issue of Le Point Veterinaire no. 236,
June 2003

Zetner K. et al. (2004) – Zur Behandlung des Gingivitis-Stomatitis-Komplexes der Katze. Erste Ergebnisse der
selektiven Wirksamkeit von Virbagen Omega. Proceedings 16. Baden-Badener Fortbildungstage, 25.-28.03.04

Addie D., Buonavoglia C., Camy G., McCann T., Gunn-Moore D., Hartmann K., Hennet P., Ishida T., Jongh O.,
Lanore D., De Mari K., Mihaljevic S-Y., Péchereau D., Régnier A., Thiry E., Vinet C. (2004) – Veterinary Interferon
Handbook. First Edition


Distemper:

Shimamura, O., Ito K., Takayama S., Kitamura Y., et Uchino T. (1999) – Therapeutic effect of feline Interferon (rFe-
IFN) on canine distemper. Proceedings of the 23rd Symposium of Japanese S.A.C. Association

Greene CE, Appel MJ. (1998) Canine Distemper. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 2nd
Edition. Philadelphia: WB Saunders Co, 1998; 9 - 22

Jongh O., Cadoré J.-L. (1994) La maladie de Carré dans l’espèce canine. Le point vétérinaire 1994 ; 25(158), 919 -
926.

Addie D., Buonavoglia C., Camy G., McCann T., Gunn-Moore D., Hartmann K., Hennet P., Ishida T., Jongh O.,
Lanore D., De Mari K., Mihaljevic S-Y., Péchereau D., Régnier A., Thiry E., Vinet C. (2004) – Veterinary Interferon
Handbook. First Edition

				
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