ALVAC (CPpp) INFORMATION 
A. ORIGIN OF THE ALVAC VECTOR 
1. Parental organism: The parent strain of canarypox (Rentschler strain) was 
isolated in Germany in 1970, and obtained by Institut Merieux in 1973. The 
virus was attenuated by 200 serial passages on chick embryo fibroblasts 
(CEFs). The attenuated virus was registered as a vaccine in France in 1975 
under the name KANAPOX (ND). Authorization was given to market the 
vaccine in France in 1982 and this was renewed in 1987 under the reference 
number 682827.2 01.82 V. The product is also licensed in Taiwan. 
2. Description of vector: The vaccine strain was sent to Select Labs from 
Institut Merieux in the fall of 1989, and then to Virogenetics. It was subjected 
to four successive plaque purifications under agar and one clone was amplified 
through five additional passages. It was designated CPpp— CanaryPox plaque 
purified, and is now referred to as ALVAC. No other genetic modifications 
were used to produce the vector. 
B. BIOLOGICAL PROPERTIES 
1. Host/ranee specificity: Productive replication of avipoxvirus is naturally 
restricted to avian species ( Recombinant Poxviruses, pl26, M. Binns ed.). 
This characteristic has been preserved in ALVAC (CPpp) and recombinants 
based on ALVAC (Appendices A, B, C, and D). In vitro it grows in CEFs 
and QT35 cells, but not in mammalian cells (Appendices A, B and C). Post- 
inoculation attempts to recover virus from the inoculation site (ID, EM, orally, 
and ocularly in squirrel monkeys) yielded virus only on days 2 and 4 post- 
inoculation, and only from ID sites at the higher dosage (Appendix E). 
Amplification of viral sequences by PCR analysis at the site of intradermal 
inoculation indicated only sporadic ability to detect the presence of virus 
beyond eleven days (Appendix E). Therefore, survival of the vector in its host 
outside the laboratory is not an issue. 
2. Virulence: ALVAC (CPpp) has the attributes of an attenuated canarypox 
virus. In vivo, it does establish infection in canaries upon skin inoculation, but 
causes no disease or death (Appendix F). In an IC challenge of newborn 
mice, ALVAC (CPpp) had an LD 50 value of 1.00 x 10 7 pfu; in 3-week-old 
mice, the LD 50 was 1.58 x 10 8 pfu (Appendix G). 
3. Immunogenicitv of ALVAC-based vectors: Despite the restriction of 
productive replication in non-avian species, ALVAC-based recombinants are 
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