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Environmental assessment for Licensing in Canada of a Live Canarypox Vector Vaccine expressing the Glycoprotein and the Nucleoprotein of Feline Leukemia Virus

For Public Release

February 7, 2008

The information in this environmental assessment was current at the time of its preparation. It is possible that the situation may have changed since that time. Please consult the VBS if you have any questions.


Table of Contents

  • Summary
  • 1. Introduction
    • 1.1 Proposed action
    • 1.2 Background
  • 2. Purpose and need for proposed action
    • 2.1 Significance
    • 2.2 Rationale
  • 3. Alternatives
  • 4. Molecular and biological characteristics of parental and recombinant organisms
    • 4.1 Identification, sources, and strains of parental organisms
    • 4.2 Source, description and function of foreign genetic material
    • 4.3 Method of accomplishing genetic modification
    • 4.4 Genetic and phenotypic stability of the vaccine organism
    • 4.5 Horizontal gene transfer and potential for recombination
    • 4.6 Host range/specificity, tissue tropism and shed/spread capabilities
    • 4.7 Comparison of the modified organisms to parental properties
    • 4.8 Route of administration/transmission
  • 5. Human safety
    • 5.1 Previous safe use
    • 5.2 Probability of human exposure
    • 5.3 Possible outcomes of human exposure
    • 5.4 Pathogenicity of parent microorganisms in humans
    • 5.5 Effect of gene manipulation on pathogenicity in humans
    • 5.6 Risk associated with widespread use of the vaccine
  • 6. Animal safety
    • 6.1 Previous safe use
    • 6.2 Fate of the vaccine in target and non-target species
    • 6.3 Potential of shed and/or spread from vaccinate to contact target and non-target animals
    • 6.4 Reversion to virulence resulting from back passage in animals
    • 6.5 Effect of overdose in target and potential non-target species
    • 6.6 The extent of the host range and the degree of mobility of the vector
    • 6.7 Safety in pregnant animals and to offspring nursing vaccinated animals
  • 7. Affected environment
    • 7.1 Extent of release into the environment
    • 7.2 Persistence of the vector in the environment / cumulative impacts
    • 7.3 Extent of exposure to non-target species
    • 7.4 Behaviour of parent microorganisms and vector in non-target species
  • 8. Environmental consequences
    • 8.1 Risks and benefits
    • 8.2 Relative safety compared to other vaccines
  • 9. Mitigative measures
    • 9.1 Worker safety
    • 9.2 Handling vaccinated or exposed animals
  • 10. Monitoring
    • 10.1 General
    • 10.2 Human
    • 10.3 Animal
  • 11. Consultations and contacts
  • 12. Conclusions and actions
  • 13. References

Summary

Canarypox-feline leukemia live recombinant vaccine consists of modified live canarypox virus (ALVAC) modified by the introduction of two copies of genes encoding the glycoprotein and the nucleoprotein of the feline leukemia virus. The feline leukemia vaccine, live canarypox vector (Purevax FeLV) for cats, (manufactured by Merial SAS., Lyon , France) has been evaluated by the Veterinary Biologics Section (VBS), Canadian Food Inspection Agency (CFIA) for licensing in Canada. As part of the requirements for licensing this product in Canada, an ‘Environmental Assessment' was conducted and a public document which contains information on the molecular and biological characteristics of the live recombinant organism, target animal and non-target animal safety, human safety, environmental considerations and risk mitigation measures prepared.

1. Introduction

1.1 Proposed action

Veterinary Biologics Section (VBS), Animal Health Division (AHD), Canadian Food Inspection Agency (CFIA) is responsible for licensing veterinary biologics for use in Canada. The legal authority for the regulation of veterinary biologics in Canada is provided under the Health of Animals Act and Regulations. Any veterinary biologic manufactured, sold or represented for use in Canada must comply with the requirements specified by the CFIA regarding safety, purity, efficacy and potency of the product. Merial Canada Inc. has submitted the feline leukemia vaccine containing a live canarypox vector, as described below, for licensing in Canada:

  • Feline Leukemia Vaccine, Live Canarypox Vector (Purevax FeLV), CFIA File 840VV/F1.7/R2.4

The Environmental Assessment was prepared by VBS as part of the overall assessment for licensing the above vaccine in Canada. CFIA consulted previously with Health Canada (HC) for the human safety aspect of this type of vaccines.

1.2 Background

The Feline Leukemia Vaccine, Live Canarypox Vector is manufactured by Merial SAS., Lyon, France, and is currently subject to a Market Authorisation by the European Commisssion. The recombinant vaccine component in this vaccine consists of live canarypox virus, modified by the insertion of genetic material encoding the glycoprotein (env gene), a portion of the reverse transcriptase (portion of the pol gene that is not expressed) and the complete nucleoprotein (gag gene) of the feline leukemia virus.

VBS has previously licensed four canarypox-based combination vaccines, consisting of live canarypox virus modified by the insertion of two canine distemper virus genes (haemagglutinin and fusion protein), for use in canines, one monovalent live canarypox virus vaccine modified by the insertion of two canine distemper virus genes (haemagglutinin and fusion protein) for use in ferrets, one monovalent and four combination vaccines containing live canarypox virus vaccine modified by the insertion of a rabies virus gene for use in cats, and one live canarypox virus vaccine modified by the insertion of a West Nile virus gene for use in horses.

Details of these products for dogs, ferrets, cats and horses are on file at VBS. In addition further information is contained within the Environmental assessment for licensing live vaccine combinations containing canine distemper vaccine, live canarypox vector in Canada (1998), the Environmental assessment for licensing live vaccine combinations containing rabies glycoprotein vaccine, live canarypox vector (2000), the Environmental assessment for licensing distemper vaccine, live canarypox vector for ferrets in Canada (2002), and the Environmental assessment for licensing West Nile vaccine, live canarypox vector in Canada (2004).

2. Purpose and need for proposed action

2.1 Significance

The label indication for Feline Leukemia Vaccine, Live Canarypox Vector is for the vaccination of healthy cats as an aid in the prevention of disease caused by feline leukemia virus.

2.2 Rationale

The VBS evaluates veterinary biologics submissions for licensure under the Health of Animals Act and Regulations. General criteria for licensure are (a) the product must be pure, safe, potent and efficacious, (b) the product must be licensed in the country of origin, (c) vaccine components must be relevant to Canadian disease conditions and (d) the product must be produced and tested in accordance with generally accepted “good manufacturing practices”. The vaccine described above, manufactured in France, met the general criteria and presented no unacceptable importation risk, and therefore was evaluated for licensure by VBS.

3. Alternatives

The two alternative options available are: (a) to issue a Permit to Import Veterinary Biologics to Merial Canada Inc. for the importation of Feline Leukemia Vaccine, Live Canarypox Vector (Purevax FeLV), if all licensing requirements are satisfactory, or (b) not to issue a Permit to Import Veterinary Biologics for the above product, if licensing requirements are not met.

4. Molecular and biological characteristics of parental and recombinant organisms

4.1 Identification, sources, and strains of parental organisms

4.1.1 Canarypox Virus

Canarypox virus is a large, enveloped double stranded DNA virus belonging to the Genus Avipoxvirus (Family: Poxviridae, Subfamily: Chordopoxviridae). Avipox viruses cause productive infections exclusively in avian species. The parent strain of the canarypox virus is known as the Rentschler strain. It was attenuated by 200 serial passages on chick embryo fibroblasts to yield the KANAPOX strain, a vaccine strain that has been licensed in France since 1982. The KANAPOX strain was subjected to four successive plaque purifications yielding the ALVAC strain of canarypox, used in the construction of this recombinant organism.

4.1.2 Feline Leukemia Virus

Feline leukemia virus is a single stranded negative RNA, type-C exogenous mammalian retrovirus, of the subfamily Oncovirinae (Family: Retroviridae). Feline leukemia affects mainly domestic cats, but can be transmitted to other wild felines. The glycoprotein, reverse transcriptase and nucleoprotein genes were obtained from the Glasgow strain of this virus. The glycoprotein induces anti-viral antibodies.

4.1.3 Vaccinia Virus

Vaccinia virus is a double stranded DNA virus belonging to the Genus Orthopoxvirus. It has been very well characterized and serves as the prototypic recombinant viral vector. In the construction of the recombinant canarypox virus, the vaccinia virus H6 promoter was cloned upstream of the glycoprotein, reverse transcriptase and nucleoprotein genes of the feline leukemia virus to direct transcription of the recombinant protein.

4.2 Source, description and function of foreign genetic material

The feline leukemia virus glycoprotein (env gene) stimulates the production of antiviral antibodies that can help to prevent the disease. The role of the antibodies against the nucleoprotein is poorly defined. There is a link between the presence of antibodies against the glycoprotein and the protection against development of clinical signs. In the construction of the recombinant canarypox, the genetic sequence for the glycoprotein, a portion of the reverse transcriptase and the complete nucleoprotein of the feline leukemia virus were inserted into the genomic DNA of a plaque purified isolate of the parent canarypox strain ALVAC; the recombinant canarypox-feline leukemia virus is known as ALVAC-FL, or CP97.

4.3 Method of accomplishing genetic modification

Details of the methods used in the construction of ALVAC-FL are on file with VBS. The identity and the purity of the ALVAC-FL has been verified using in situ plaque hybridization and restriction analysis of the viral DNA to screen for the absence of parental canarypox virus. The expression of the glycoprotein and nucleoprotein genes of the feline leukemia virus in cells infected with the recombinant canarypox-feline leukemia virus was confirmed by immunoprecipitation of glycoprotein from infected cellular extracts, and by indirect immunofluorescence. In both instances, specific monoclonal antibody against feline leukemia virus was used for the detection. The manufacturer established a Master Seed stock of the recombinant organism; this was tested for the absence of mammalian and avian extraneous agents, purity and safety according to tests described in the European Pharmacopoeia. These data have been reviewed and are on file at VBS.

4.4 Genetic and phenotypic stability of the vaccine organism

No gross genetic or phenotypic alterations were detected after 20 cell culture passages of a similar recombinant vaccine ALVAC-RG (Environmental assessment for licensing vaccine combinations containing rabies glycoprotein vaccine, live canarypox vector [2000]).

4.5 Horizontal gene transfer and potential for recombination

Recombination as a result of molecular interaction between poxviruses within co-infected cells was reported by Moss (1992). Such a recombination may result in novel modified live viruses which may lead to changes in the virulence of the affected virus. The likelihood of horizontal gene transfer and recombination is likely to be very low as the canarypox virus does not replicate in the feline host.

4.6 Host range/specificity, tissue tropism and shed/spread capabilities

Avipoxviruses are restricted in their host range (ie. potential to replicate) to avian species. Canarypox virus is known to infect canaries, ducks, chickens, turkeys and pigeons (Tripathy and Cunningham, 1984) but the host range may not be limited to these species. In canaries, wild type canarypox virus causes local pox lesions and death. In pigeons, wild canarypox virus causes generalized infections and local lesions while in chickens, turkeys and ducks it causes only localized lesions. Localized lesions of canarypox usually occur in the skin, on comb and wattles, and are characterized by distinct white/yellow nodules. In the generalized form of the disease, diphtheritic lesions occur in the mucous membranes of the mouth, oesophagus and trachea of birds with respiratory signs.

4.7 Comparison of the modified organisms to parental properties

The host range of ALVAC and the recombinant organism ALVAC-RG is expected to be the same as the parental canarypox vaccine strain. However, ALVAC has the attributes of an avirulent canarypox virus causing infection and skin lesions in canaries upon skin inoculation but no disease nor death.

4.8 Route of administration/transmission

Avian poxviruses such as canarypox are transmitted mechanically from infected birds by aerosols, animal handlers, mosquitoes, and mites. Poxviruses are typically capable of surviving for long periods in the environment particularly in dried scabs (Tripathy and Reed, 1997).

5. Human safety

As part of the safety assessment of other recombinant vaccines with the same canarypox vector (ALVAC), regulators at HC, reviewed the human safety data supplied by Virogenetics Corporation, Troy, New York and Merial Inc., Atlanta, Georgia. Following the assessment, HC indicated that there is no objection from the human safety aspect to the use of the above canarypox vector vaccines in cats.

5.1 Previous safe use

Several ALVAC based recombinants have been used in phase I human clinical trials (Taylor et al., 1994; Plotkin et al., 1995; Paoletti, 1996, Fries et al., 1996; Marshall et al., 1999). ALVAC-RG has been administered safely to human volunteers (Cadoz et al., 1992; Fries et al., 1996). Phase I trials with ALVAC based experimental recombinant vaccines against human immunodeficiency virus have also been reported (Pialoux et al., 1995; Fleury et al., 1996; Coeffier et al., 1997; Clements-Mann et al., 1998).

5.2 Probability of human exposure

Human exposure to the vaccine is likely to be limited to veterinarians, animal technicians, manufacturing staff and testing laboratory staff.

5.3 Possible outcomes of human exposure

Canarypox virus is not a zoonotic agent and is not expected to affected human health. Upon intramuscular injection of human volunteers with an ALVAC based recombinant rabies vaccine, mild transient local reactions such as tenderness and discomfort as well as systemic complaints such as mild headache and fatigue have been observed (Fries et al., 1996).

5.4 Pathogenicity of parent microorganisms in humans

Several ALVAC recombinant constructs derived from the Rentschler strain of canarypox have been tested in humans; see section 5.1.

5.5 Effect of gene manipulation on pathogenicity in humans

Recombinant canarypox-feline leukemia vaccine is not pathogenic in humans; see section 5.1.

5.6 Risk associated with widespread use of the vaccine

The widespread use of the vaccine is not expected to have any public health significance.

6. Animal safety

6.1 Previous safe use

Safety of the recombinant virus ALVAC has been demonstrated experimentally in humans, cats, dogs, canaries, chickens, primates (squirrel monkeys, cynomolgus monkeys, chimpanzees, macaques), and rodents. These data are on file at VBS. The manufacturer has also provided laboratory and field safety data for the recombinant virus ALVAC-FL for over 1700 cats.

6.2 Fate of the vaccine in target and non-target species

Backpassage studies in cats have demonstrated that ALVAC-FL is unlikely to revert to virulence. The vaccine does not replicate in the targeted feline animals. There are no reports of avipoxviruses causing productive infection in species other than the avian species. The vaccine is not shed after subcutaneous vaccination of mammals, therefore birds in the veterinary clinic should not be at risk. In a reversion to virulence study six kittens seronegative for the recombinant virus ALVAC-FL were vaccinated subcutaneously with a dose corresponding to 10 times the release dose. No virus shedding was detected from samples of saliva, urine and feces collected on days 0, 1, 2, 3, 4, 5, and 7. In another experiment, intradermal injection of the vaccine organism to mice and guinea pigs did not cause local reaction at the injection site and no systemic reactions were observed. The manufacturer also provided reports of safety studies conducted in squirrel monkeys, cynomolgus monkeys, dogs, canaries, and chickens; these reports are on file at VBS.

6.3 Potential of shed and/or spread from vaccinate to contact target and non-target animals

Since no recombinant canarypox-feline leukemia virus was detected in the saliva, urine and feces after parenteral inoculation, it is not expected that there will be excretion and propagation of the virus following contact with target and non-target animals.

6.4 Reversion to virulence resulting from back passage in animals

Since no recombinant canarypox-feline leukemia virus (ALVAC-FL) was detected in the excretions of inoculated kittens, consecutive back-passages in other kittens could not be achieved.

6.5 Effect of overdose in target and potential non-target species

Overdose testing (10 times the recommended dose) was done in kittens. The animals remained clinically healthy following vaccination.

6.6 The extent of the host range and the degree of mobility of the vector

Canarypox virus is restricted in its host range to avian species. Since recombinant ALVAC-FL virus is not shed from vaccinated cats, no spread of the organism is expected.

6.7 Safety in pregnant animals and to offspring nursing vaccinated animals

Since ALVAC-FL does not replicate and shed in mammalian hosts, the safety profile of the vaccine is not expected to be different for pregnant animals and offspring nursing vaccinated animals.

7. Affected environment

7.1 Extent of release into the environment

The feline leukemia vaccine - live canarypox vector would only be used in veterinary clinics. The recombinant vaccine organism is not shed by the vaccinated animals. Potential for occasional environmental release through accidental spills, unintended syringe aerosols and contamination of the skin and hair around the vaccination site does exist during routine use of these vaccines in veterinary clinics.

7.2 Persistence of the vector in the environment / cumulative impacts

Poxviruses are capable of surviving for extended periods of time under normal environmental conditions, especially in association with dried scab material and protected from direct sunlight (Tripathy and Reed, 1997). Desiccated poxviruses are extremely resistant to environmental conditions. The survival characteristics of the recombinant canarypox-rabies are not predicted to be different from the parent poxvirus.

7.3 Extent of exposure to non-target species

Extent of exposure to non-target species is expected to be low since the vaccine administration occurs in a clinical setting and the vaccinates do not shed the virus.

7.4 Behaviour of parent microorganisms and vector in non-target species

Recombinant ALVAC-FL virus is restricted in its host range to avian species and will not develop a productive infection in non-avian species. In avian species, the ALVAC-FL virus resembles an attenuated canarypox virus by causing skin infections in canaries upon skin inoculation but does not cause death. Wild type canarypox virus is capable of causing death in canaries following skin inoculation (Tripathy and Cunningham, 1984).

8. Environmental consequences

8.1 Risks and benefits

For any vaccine, risks of vaccination can be attributed to potential adverse reactions. Occasional adverse reactions such as transient lethargy, mild fever, and inflammatory or hypersensitive types of reactions have been noted in cats vaccinated with vaccine combinations containing ALVAC-FL. This risk is identified on the product label along with a recommended treatment regimen that may include antihistamines, anti-inflammatories, and/or epinephrine. The benefit of the vaccine is its ability to help in the prevention of the infection in cats as demonstrated in vaccination-challenge studies on file in VBS.

8.2 Relative safety compared to other vaccines

The recombinant canarypox ALVAC-FL contains genes encoding the glycoprotein, a portion of the reverse transcriptase and the complete nucleoprotein of the feline leukemia virus expressed off the vaccinia virus H6 promoter. ALVAC-FL does not have the ability to cause feline leukemia or localized and systemic vaccinia-type lesions. Inability to cause disease following vaccination, adjuvant-free administration and lack of potential for reversion to virulence are positive safety features of ALVAC-FL.

9. Mitigative measures

9.1 Worker safety

The vaccine will be manufactured at Merial SAS, Lyon, France, a veterinary biologics establishment authorized by the European Commission. Individuals working with the vaccine either in the production facility or veterinarians and animal technicians working in veterinary clinics can be exposed to the live recombinant organism. Since avipoxviruses cannot cause productive infections in humans, such exposure is not considered to be a safety concern.

9.2 Handling vaccinated or exposed animals

Exposure of groups such as cat owners to the live recombinant organism is likely to be very low since vaccinated animals do not shed the virus and unintended contamination of hair and skin at the vaccination site is not considered to be of public health significance.

10. Monitoring

10.1 General

The vaccine licensing regulations in Canada require manufacturers to report all suspected adverse reactions to CFIA within 15 days of receiving notice from an owner or a veterinarian. Veterinarians may also report suspected adverse reactions directly to the CFIA. On VBS receipt of an adverse reaction complaint, the manufacturer is asked to investigate and prepare a report for the owner's veterinarian and CFIA. If the problem is resolved to the satisfaction of the veterinarian/client, no further action is usually requested by VBS. However, if the investigation is not satisfactory, VBS may initiate regulatory action depending on the case which may include further safety testing, temporary stop sale or product withdrawal from the market.

10.2 Human

No special monitoring of the human safety of the product will be carried out.

10.3 Animal

Veterinarians/cat owners and manufacturers should report any suspected adverse events to VBS as indicated above. For reporting purposes, adverse events are divided into Type 1, 2, and 3 reactions. Type 1 reactions are defined as any systemic adverse reaction, anaphylactic or hypersensitivity requiring veterinary treatment including: persistent fever, recumbency, persistent lethargy, decrease in activity, muscle tremors, shivering, hypersalivation, dyspnea and other respiratory problems, cyanosis, diarrhea, vomiting, colic and other gastrointestinal problems, eye problems, abortions and other reproductive problems and neurological signs. Type 2 reactions are defined as death following vaccination. Type 3 reactions are defined as local persistent reactions such as edema, abscess, granuloma, fibrosis, alopecia, hyperpigmentation and excessive pain at the injection site. Suspected adverse events should be reported using the form Notification of Adverse Events to Veterinary Biologics (CFIA/ACIA 2205).

11. Consultations and contacts

Human health

Health Canada
Tunney's Pasture, Mail Stop: 2201E
Ottawa, Ontario K1A 0K9

Importer

Merial Canada Inc.
20000 Clark-Graham
Baie D'Urfé, Québec H9X 4B6

Manufacturer

Merial SAS
29 Tony Garnier Avenue - Box 7123
69348 Lyon Cedex 07
France

12. Conclusions and actions

Following this assessment, the Permit to Import Veterinary Biologics will be issued by Merial Canada Inc., Québec, to allow importation of the following product from the manufacturer Merial SAS, Lyon, France:

  • Feline Leukemia Vaccine, Live Canarypox Vector (Purevax FeLV), CFIA File 840VV/F1.7/R2.4

13. References

Clements-Mann, M.L., K. Weinhold, T.J. Matthews, B.S. Graham, G.J. Gorse, M.C. Keefer, M.J. McElrath, R.H. Hsieh, J. Mestecky, S. Zolla-Pazner, J. Mascola, D. Schwartz, R. Siliciano, L. Corey, P.F. Wright, R. Belshe, R. Dolin, S. Jackson, S. Xu, P. Fast, M.C. Walker, D. Stablein, J. L. Excler, J. Tartaglia, and E. Paoletti (1998). Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group. J. Infect. Dis. 177:1230-1246.

Coeffier, E., J.L. Excler, M.P. Kieny, B. Meignier, C. Moste, J. Tartaglia, G. Pialoux, D. Salmon-Ceron and C. Leclerc (1997). Restricted specificity of anti-V3 antibodies induced in humans by HIV candidate vaccines. AIDS Res Hum Retroviruses 17:1471-1485.

Fleury, B., G. Janvier, G. Pialoux, F. Buseyne, M.N. Robertson, J. Tartaglia, E. Paoletti, M.P. Kieny, J.L. Excler and Y. Riviere (1996). Memory cytotoxic T lymphocyte responses in human immunodeficiency virus type 1 (HIV-1)-negative volunteers immunized with a recombinant canarypox expressing gp 160 of HIV-1 and boosted with recombinant gp 160. J. Infect. Dis. 174:734-738.

Fries, L.F., J. Tartaglia, J. Taylor, E.K. Kauffman, B. Meignier, E. Paoletti, and S. Plotkin (1996). Human safety and immunogenicity of a canarypox-rabies glycoprotein recombinant vaccine: an alternative poxvirus vector system.

Marshall, J.L., M.J. Hawkins, K.Y. Tsang, E. Richmond, J.E. Pedicano, M.Z. Zhu, and J. Schlom (1999). Phase I study in cancer patients of a replication-defective avipox recombinant vaccine that expresses human carcinoembryonic antigen. J. Clin. Oncol. 17:332-337.

Merial (December 1998). Purevax FeLV - Live recombinant vectored vaccine against feline leukemia. - The environmental risk assessment resulting from the information provided under points IIH.1. to II.H.4 above; Safety dossier - Part III -E.Ecotoxicity (No. 1017/CEE-01).

Moss, B. 1992. Molecular biology of poxviruses. In Recombinant Poxviruses, edited by M.B. Binns and G.L. Smith, CRC Press, Florida. pp 45-80.

Paoletti, E. (1996). Application of pox virus vectors to vaccination: an update. Proc. Natl. Acad. Sci. USA 93:11349-11353.

Pedersen, N.C. (1987). Virus Infections of Carnivores. Chapter 30 in : Virus Infections of Vertebrates, ed. M.J. Appel, Elsevier Science Publishers B.V.

Pialoux, G., J.L. Excler, Y. Reviere, G. Gonzales-Canali, V. Feuillie, P. Coulaud, J.C. Gluckman, T.J. Matthews, P. Meignier, M.P. Kieny, P. Gonnet, I. Diaz, C. Meric, E. Paoletti, J. Tartaglia, H. Solomon and S. Plotkin, (1995). A prime-boost approach to HIV preventive vaccine using a recombinant canarypox virus expressing glycoprotein 160 (MN) followed by a recombinant glycoprotein (MN/LAI). The AGIS Group, and l'Agence Nationale de Recherche sur la Sida. AIDS Research and Human Retroviruses 11:373-381.

Plotkin, S.A., M. Cadoz, B. Meignier, C. Meric, O. Leroy, J.L. Excler, J. Tartaglia, E. Paoletti, E. Gonczol and G. Chappuis. 1995. The safety and use of canarypox vectored vaccines. Dev. Biol. Stand. 84:165-170.

Rhone Merieux, Inc. (November 6, 1996) Risk analysis for a canarypox-vector rabies vaccine (CP65A) for cats. Research Report: recRAB 96/073.

Tatarglia, J., Jarrett, O., Neil, J.C., Desmettre, P. and Paoletti, E. (1993). Protection of cats against feline leukemia virus by vaccination with a canarypox virus recombinant, ALVAC-FL. J. Virol., 67: 2370-2375.

Taylor, J., J. Tartaglia, M. Riviere, C. Duret, B. Languet, G. Chappuis and E. Paoletti. 1994. Applications of canarypox (ALVAC) vectors in human and veterinary vaccination. Dev. Biol. Stand. 82:131-135.

Tripathy, D.N. and C.H. Cunningham (1984). Avian pox. In Diseases of Poultry, 8e éd., revue par M.S. Hofstad, H.J. Barnes, B.W. Calnek, W.M. Reid et H.W. Yoder Jr., Iowa State University Press, Iowa. pp 524-534.

Tripathy, D.L. and Reed, W.M. 1997. Pox. In Diseases of Poultry, 10th edition, edited by B.W. Calnek, H.J. Barnes, C.W. Beard, L.R. McDougald and Y.F. Saif. Iowa State University Press, Iowa. pp 643-659.

Environmental assessment for licensing vaccine combinations containing canine distemper vaccine, live canarypox vector in Canada. VBS, CFIA. 1998-06-15.

Environmental assessment for licensing vaccine combinations containing rabies glycoprotein vaccine, live canarypox vector in Canada. VBS, CFIA. 2000-03-28.

Environmental assessment for licensing distemper vaccine, live canarypox vector for ferrets in Canada. VBS, CFIA. 2002-09-04.

Environmental assessment for licensing West Nile vaccine, live canarypox vector in Canada. VBS, CFIA. 2004-04-30.


Prepared and revised by:

Veterinary Biologics Section
Animal Health Division
Canadian Food Inspection Agency