THE POXVIRUS VECTORS - E. PAOLETTI 
VIROGENETICS 
VIROGENETICS CORPORATION 
465 JORDAN ROAD 
RENSSELAER TECHNOLOGY PARK 
TROY, NY 12180 USA 
TEL (518) 283-8389 
FAX (518) 283-0936 
January 8, 1993 
Dr. Nelson Wivel, Director 
Office of Recombinant DNA Activities 
National Institutes of Health 
Building 31, Room 4B11 
Bethesda MD 20892 
Dear Dr. Wivel: 
This letter is to formally initiate a request for reduction in required Biosafety Level for three 
of our poxvirus vectors, NYVAC, ALVAC, and TROVAC. We wish to present our 
proposal to the RAC at the March 2, 1993 meeting. 
The Office of Recombinant DNA Activities (ORDA) recognizes that several different 
combinations of laboratory practices, containment equipment, and laboratory design may be 
appropriate for containment of specific research activities. The selection of alternative 
methods of primary containment is dependent on the level of biological containment provided 
by the host-vector system ( Guidelines for Research Involving Recombinant DNA Molecules , 
Appendix G-II ). We are asking for a reduction in containment level for three of our 
recombinant poxviruses, NYVAC, ALVAC and TROVAC from BL-2 to BL-1 because we 
believe they "do not present a significant risk to health or environment" (Ibid, Section IV-C), 
due to the extent of biological containment provided by their construction. Such a change in 
classification would more accurately reflect the pathogenicity of the organisms and their 
potential hazard to man, as well as facilitate the development of safe and efficacious human 
and veterinary vaccines based on these vectors. 
According to the Guidelines, any combination of vector and host which is to provide 
biological containment must be chosen or constructed so that the following types of "escape" 
are minimized: 
i) survival of the vector in its host outside the laboratory 
ii) transmission of the vector from the host to other non-laboratory hosts 
We will demonstrate minimization of these types of "escape" for both vectors, via biological 
containment, to a degree which we believe justifies the reduction in biosafety level we are 
requesting. 
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Recombinant DNA Research, Volume 18 
