Delivering attenuated lentivirus vaccines as proviral DNA would be simple a
nd inexpensive. Inoculation of macaques with wild-type simian immunodeficie
ncy virus strain mac239 (SIVmac239) DNA or SIVmac239 DNA containing a singl
e deletion in the 3' nef-long terminal repeat overlap region (nef/LTR) led
to sustained SIV infections and AIDS. Injection of SIVmac239 DNA containing
identical deletions in both the 5' LTR and 3' nef/LTR resulted in attenuat
ed SIV infections and substantial protection against subsequent mucosal SIV
mac251 challenge.