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<body><p class="default_Text"><b>Environmental Assessment</b></p>
<p class="default_Text"><b>For Field Testing </b></p>
<p class="default_Text"><b>Feline Leukemia Vaccine, Live Canarypox Vector</b></p>
<p class="default_Text"><b>I</b>.
<b>Proposed Action</b></p>
<p class="default_Text">APHIS is considering granting authorization to ship an unlicensed Feline Leukemia Vaccine, Live Canarypox Vector, for field safety testing.  Merial, Inc., Athens, Georgia, has requested authorization to conduct field tests under normal feline husbandry practices in the United States.</p>
<p class="default_Text">Under the provisions of the Virus-Serum-Toxin Act of 1913, as amended in 1985, the USDA must ensure that veterinary biologics are pure, safe, potent, and efficacious and not worthless, contaminated, dangerous, or harmful.  Accordingly, APHIS has conducted a risk analysis and has concluded that the safety risks to animals, public health, and the environment are low.  A copy of the firm’s risk analysis with confidential business information removed is available upon request.  The APHIS risk analysis includes this document, but also incorporates review of all the firm’s studies and tests, the confirmatory testing completed by APHIS personnel on the Master Seed Virus to confirm purity, identity, and expression of immunogenic protein, consultation with subject matter experts as needed, results of literary and regulatory review, and comparison with similar previously tested or licensed products.</p>
<p class="default_Text"><b>II.
Background
</b></p>
<p class="default_Text">Feline Leukemia virus (FeLV) is a major cause of morbidity and mortality in domestic cats and a few other Felidae (1).  It is present worldwide.  Persistently-infected domestic cats are the major reservoir for feline leukemia.  The virus is excreted primarily in saliva, but also tears, urine, and feces of infected cats.  Transmission of the virus from cat to cat is facilitated by prolonged contact with an infected cat.  FeLV causes a number of clinical syndromes associated with immunosuppression and a variety of malignancies may result.
</p>
<p class="default_Text">The experimental vaccine to be used in the proposed field tests is a live recombinant virus consisting of the canarypox vector (ALVAC) derived from an attenuated vaccine strain of canarypox virus (KANAPOX®), and encoding certain modified sequences of FeLV.  Current USDA-licensed vaccines using the ALVAC vector are vaccines for canine distemper, equine influenza (HA genes from several strains), feline rabies, FeLV, and West Nile virus.  </p>
<p class="default_Text">The proposed field safety test will be conducted in at least three different geographical locations and the product will be used according to instructions on the product circular.  The potential for escape and dispersal of the experimental vaccine from the proposed release sites is low.  The personnel to conduct the study are experienced in feline health management.
</p>
<p class="default_Text"><b>III.
Need for the Proposed Action</b></p>
<p class="default_Text">The recombinant vaccine is for use in healthy cats as an aid in prevention of disease due to FeLV.  It is very similar to an already licensed Feline Leukemia Vaccine, Live Canarypox Vector from Merial, Inc. in regard to the nature of the inserted coding sequences, the sites of insertion, and the promoters used.  The new vaccine has minor changes that improve expression and the immune response generated.  The first FeLV vaccine, licensed in 2004, has been used in North American markets since then and in Europe since 2001 without safety issues.  The new vaccine is expected to have a comparable safety profile but be an improvement on the first vaccine.
</p>
<p class="default_Text"><b>IV.
Areas of Concerns
</b></p>
<p class="default_Text">The three areas of concern to APHIS are:  1) animal safety, 2) public health, and 3) environmental safety.  APHIS has conducted its own risk analysis to assess whether risks are associated with the proposal to field test this experimental vaccine.  The safety characteristics of this vaccine have been thoroughly evaluated.  The conclusions derived from the risk analysis for each of the areas of concern are summarized below.
</p>
<p class="default_Text">
<b>A.
Animal Safety</b></p>
<p class="default_Text">The risk to animals is low.  </p>
<p class="default_Text">1.  The host range of avipoxviruses in general, and the ALVAC backbone in particular, is highly restricted.  Exposure of canaries to this FeLV vaccine may lead to infection and seroconversion but no adverse reactions.  Exposure of other species to the vaccine will result in no detectable sign of exposure, except possible development of antibodies if exposed by the parenteral route.  
</p>
<p class="default_Text">2.  The firm has conducted animal safety studies in cats and mice using the vaccine and in cats, guinea pigs, mice, chickens, and canaries using the closely-related, licensed FeLV vaccine, with satisfactory results. </p>
<p class="default_Text">3.  Back passage and shed-spread studies using the licensed FeLV vaccine demonstrated that the vaccine virus would be extremely unlikely to replicate, revert to virulence, or be shed after injection in cats.</p>
<p class="default_Text">4.  Results from restriction endonuclease analysis, southern blotting, and sequence analysis of the MSV and MSV+5 were consistent with genetic stability of the vaccine virus.  Immunoplaque expression assays supported phenotypic stability.
</p>
<p class="default_Text">5.  Recombination between vaccine and wild-type poxvirus is very unlikely in the cat and most non-target species because those species are only rarely infected by poxviruses.  Also, ALVAC constructs do not replicate in most species, excluding avian species.  Should recombination occur, the likely result would be the rapid predominance of the wild-type strain over the recombinant, since the inserted FeLV sequences provide no competitive advantage for survival.
</p>
<p class="default_Text">
<b>B.
Public Health
</b></p>
<p class="default_Text">The risk to public health is likewise low.  </p>
<p class="default_Text">1. The ALVAC backbone was classified as a Risk Group 1 agent by the NIH Recombinant DNA Advisory Committee (2), or an agent “not associated with disease in healthy adult humans”.</p>
<p class="default_Text">2. The firm conducted <i>in vitro</i> replication studies that indicated ALVAC grows in chicken embryo fibroblast (CEF) cells and in the quail fibroblast cell line, but not in human cell lines nor in mammalian cell lines.</p>
<p class="default_Text">3. In addition to safe use of ALVAC-vectored recombinants in animals, several ALVAC constructs have been tested in humans without adverse effect, including vaccines for rabies, measles, Cytomegalovirus, HIV, and Japanese encephalitis virus.</p>
<p class="default_Text">4. Only qualified personnel administering the recombinant vaccine will be exposed to it.  Although the safety of this specific FeLV vaccine has not been evaluated in humans and is therefore unknown, accidental human injection is not expected to cause adverse effects, since ALVAC has a limited avian host range and is nonpathogenic in those species.
</p>
<p class="default_Text">C. <b>Environmental Safety
</b></p>
<p class="default_Text">The risks to the environment are low.  </p>
<p class="default_Text">1. Shed-spread studies with other recombinants prepared from the same ALVAC backbone in mammals and avian species other than canaries indicate that the ALVAC recombinant viruses are not shed, thus not spread into the environment. </p>
<p class="default_Text">2. No genes of the vaccine are known to be virulent and no toxins are produced. </p>
<p class="default_Text">3. The vaccine is for parenteral use in cats and, thus, administration of the vaccine will not result in environmental release, given the lack of replication and shed/spread of the virus in cats.
</p>
<p class="default_Text">4. Avipoxviruses can be mechanically transmitted primarily by mosquitoes, but there is no evidence of replication in the insect vector or transmission to non-avian species.  Studies on the canarypox-vectored West Nile virus vaccine indicated no evidence of viral replication in the four mosquito species studied.</p>
<p class="default_Text">5. Avipoxviruses are readily inactivated by heat (i.e. 30 minutes at 50oC or 8 minutes at 60oC), alkali, and disinfectants (e.g. chlorhexidine, bezalkonium chloride, formaldehyde, bleach).</p>
<p class="default_Text">There are no apparent substantial issues with adverse environmental impacts concerning this vaccine.</p>
<p class="default_Text"><b>V.
Alternatives</b></p>
<p class="default_Text">Two alternatives were considered.  The only alternative considered other than the preferred action alternative is not to approve the proposed field tests, the “no action” alternative.  We have considered the applicants’ goals in light of the agency’s public interest and responsibilities and any potential environmental impact.  Based upon the results of our risk analysis and the potential applications for this vaccine in disease control, APHIS adopts the alternative that the proposed field tests be approved.
</p>
<p class="default_Text"><b>VI.
Conclusion</b></p>
<p class="default_Text">Based upon the risk analysis documented in this EA, APHIS has determined that implementation of the proposal would not significantly affect the quality of the human environment and that the preparation of an Environmental Impact Statement is not required (Finding of No Significant Impact).</p>
<p class="default_Text"><b>References</b></p>
<p class="default_Text">1. Feline Leukemia Virus and Related Diseases: Introduction. In: The Merck Veterinary Manual, Ninth Edition, 2008. C.M. Kahn, (Ed), Merck & Co., Inc., Whitehouse Station, N.J. Available online: <a href="http://www/merckvetmanual.com"><u>http://www/merckvetmanual.com</u></a></p>
<p class="default_Text">2. NIH Recombinant DNA Advisory Committee, 7-8 June 1993; <i>Federal Register</i>, Sep 13, 1993;58(175):47910. </p>
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