Galpin/DA/N2 niBenv 
stages of HIV-1 infection 16 . It is apparent, however, that immune responses resulting from 
natural HIV infection are ultimately inadequate for stabilization or recovery, perhaps because 
of suboptimal viral antigen presentation (e.g., down-regulation of MHC) 17 by virus-infected 
cells. More potent HIV-specific CTL activity may have a significant impact on halting HIV 
disease progression because CTL are capable of eliminating virus-infected cells, the reservoir 
of replicating HIV. 
Conventional product strategies (inactivated virus, soluble proteins) characteristically 
elicit humoral antibody responses, whereas live attenuated viral products appear to induce 
both potent antibody and cellular immune responses. The effectiveness of attenuated viral 
products is likely attributable in part to their ability to provide foreign viral proteins to the 
intracellular antigen processing pathways for effective CTL activation. However, the use of 
live attenuated viral products presents significant safety concerns, particularly regarding HIV. 
Therefore, alternative approaches, such as the use of HIV-IT (V), may provide for more 
consistent CTL activation and is important to test these effects in combating HIV disease 
progression. 
Viral infection and intracellular synthesis of viral proteins are usually required for in 
vivo priming of CD8 + , Class I MHC-restricted CTL 18 - 19 - 20 - 21 . In contrast, inactivated virus 
and soluble proteins do not consistently induce CTL in vivo 22 . Endogenously synthesized 
foreign proteins in virus-infected cells are degraded within the cytoplasm into protein 
fragments that associate with Class I MHC. This antigen-MHC complex, when transported 
to the cell surface, can lead to activation of CD8 + CTL. 
Retroviral vectors are very efficient at introducing genes into host cells, and thus, 
represent an effective means of providing foreign antigens to the intracellular antigen 
16 Tsubota, H. et al„ J. Exp. Med., 169:1421-1434 (1989). 
17 Scheppler, J.A. et al., J. Immunol., 143:2858-2866 (1989). 
18 Townsend, A.R., et al.. Cell, 42:457-467 (1985). 
19 Braciale, T.J., et al., Immunol. Rev., 98:95-114 (1987). 
20 Moore, M.W., et al., Cell, 54:777-785 (1988). 
21 Townsend, A., et al., Nature, 334:443-448 (1989). 
22 Bevan, M.J. Nature, 342:478 479 (1989). 
Recombinant DNA Research, Volume 17 
[865] 
