'/IROGENETICS 
capable of expressing extrinsic immunogens and eliciting humoral and cellular 
immune response in mice, cats, dogs and swine (Appendices H, I, J, & K). In 
four- to six-week-old mice, ALVAC-RG (vCP65) had a PD 50 value of 3.86 
TCID 50 (Appendix G). Immunization with ALVAC (CPpp) or other ALV AC- 
based recombinants does not preclude immune responses to novel antigens 
expressed by the ALVAC vector (Appendix L). 
4. Environmental distribution; It is anticipated that the ALVAC (CPpp) strain 
of canarypox virus will have the same range of environmental distribution as 
the Rentschler vaccine strain from which it was derived. Due to the avian- 
restricted host-range of ALVAC (CPpp), no horizontal transmission from 
mammal to mammal, or vertical transmission from mammal to avian is 
anticipated. 
ALVAC-RG (vCP65), a recombinant rabies vaccine expressing the rabies 
glycoprotein G, is in Phase 1 human clinical trial at Johns Hopkins (Appendix 
M) and in France (Appendix N). The vaccine was assessed as being safe 
without any instances of significant systemic illness, significant adverse 
reactions at the injection site, significant classic laboratory abnormalities, or 
death in any of the human volunteers. 
ALVAC-gpl60 MN (vCP125), an HTV-1 vaccine, and ALVAC-MV (vCP82), 
a measles vaccine, are both in Phase 1 human clinical trials in France. 
The USD A/ APHIS has assigned Biosafety Level- 1 to a contained release 
involving an ALV AC-based Japanese Encephalitis Virus vaccine (vCP107) to 
be administered to 150 swine at Purdue University (Appendix O). 
5. Geographical distribution: The ALVAC (CPpp) vector has the potential to 
be used as a vaccine for a wide variety of both human and veterinary diseases 
world-wide. The highly attenuated phenotype of the ALVAC vector coupled 
to its potency as an immunization vehicle provides a favorable benefit-to-risk 
ratio. It possesses the advantages of vaccinia-based vaccine candidates, yet has 
attenuation characteristics consistent with an enhanced safety profile. 
6 . Recommended NIH/CDC Biosafety Level: The NIH/CDC recommended 
Biosafety Level for avipox viruses is Biosafety Level 2. Due to the attenuated 
nature of ALVAC (CPpp), the demonstration of non-replication in mammalian 
species, the safety data presented for both ALVAC (CPpp) and ALVAC-based 
recombinants, and the approval of Phase I human clinical trials of ALVAC-RG 
(vCP65), ALVAC-MV (vCP82), and ALVAC-gpl60 MN (vCP125), we are 
requesting reduction to Biosafety Level 1. 
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