Recombinant DNA Advisory Committee - 3/3-4/94 
NIH Guidelines. Under Version B, Dr. Richard Haubrich's human gene transfer 
experiment (Protocol #9312-062) would have been exempt from RAC review. Dr. 
Haubrich's study involved the intramuscular injection of the retrovirus vector, HIV- 
IT(V), which encodes HTV-l IIIB env. Version B would require long-term expression 
vaccines, e.g., certain influenza vaccines to be submitted for full RAC review. 
Dr. Straus compared the differences between Versions A and B of Footnote 21: (1) 
Version B includes the term "human studies," which narrows the definition. (2) Version 
B includes the term "microbial immunogen," which limits the exemption to microbial 
immunogens and excludes other gene products. (3) Version A deletes the term 
"therapeutic," since the majority of vaccines are intended for prophylactic rather than 
therapeutic purposes. (4) Version B includes the term "persistence." Dr. Straus 
expressed his concern that the RAC should not exempt experiments in which the vector 
would persist or encode immunogens other than those of microbial origin. Dr. Post 
asked if the term "microbial" would encompass viruses. Dr. Straus responded that viruses 
would be considered "microbial." 
Dr. Straus disagreed with Dr. Parkman's interpretation of the term "persistence." 
"Persistence" would be defined as biochemical persistence of the vector, not the immune 
response. Herpesviruses and adenoviruses are capable of long-term persistence in the 
body; therefore, not all constructs involving these viruses should be considered exempt. 
Dr. Walters asked whether Version B expands the scope of RAC review, e.g., including 
adenovirus vaccines, that have not been reviewed by the RAC previously. Dr. Straus 
acknowledged that Version B would exclude adenovirus vaccines; therefore, RAC review 
would be required. Ms. Grossman expressed her concern about adenovirus vectors. The 
wild-type virus persists in lymphocytes and different mutations of the virus introduced 
during construction of adenovirus vectors affect its persistence and immunological 
activity in the human body. Dr. Parkman agreed that these are reasons that adenovirus 
vectors should be reviewed by the RAC. Dr. Straus emphasized that advances in 
technology pose new safety issues, and that he would favor that these issues be resolved 
by the RAC in the public forum before exempting these vaccine constructs. Dr. Post 
said that vaccines exempted from the RAC review will still need to be approved by 
another government agency. Dr. Parkman explained that the majority of the 
recombinant viral vaccines that exhibit transient expression will be exempt from RAC 
review, e.g., poxvirus vectors. However, virus vectors that have the potential to persist in 
the body will not be exempt from RAC review, e.g., retroviruses, adenoviruses, 
herpesviruses, and papovaviruses. Vaccines involving persistent viruses may be 
encompassed by the Accelerated Review process that is proposed as a separate agenda 
item for this meeting. 
Committee Motion 
A motion was made by Dr. Carmen and seconded by Ms. Grossman to approve Version 
B definition of Footnote 21 of the NIH Guidelines (exempt recombinant DNA vaccines). 
The motion to accept Version B passed by a vote of 13 in favor, 0 opposed, and no 
abstentions. 
Recombinant DNA Research, Volume 19 
[37] 
