We earlier reported that immunization of macaques with a
reverse transcriptase-deleted SHIV(KU2) (DeltartSHIV(KU2)) plasmid that contained HIV-1(HXB2) env and SIV gag-nef induced protection against
AIDS caused by challenge virus SHIV89.6P with a heterologous env. We further deleted vif and
integrase from DeltartSHIV(KU2) and substituted the 3'LTR with SV40
poly A sequences, creating Delta4SHIV(KU2) (M) and a parallel construct containing gag-nef of HIV-1(SF2), Delta4SHIV(KU2) (H). Six macaques received two
intramuscular injections of the (M)
DNA, and another six received three
injections of the (
H) DNA. Three of the latter group received two post-challenge boosts with (M)
DNA vaccine. Seven virus control macaques were inoculated with SHIV89.6P. All twelve immunized macaques were challenged with SHIV89.6P virus, and CMI responses were measured by ELISPOT assays. Virus control animals all developed progressive
infection, whereas vaccinated macaques from both groups controlled virus replication, with plasma viral loads dropping to undetectable levels between weeks 6 and 126 p.i. This
DNA vaccine was efficacious even though it encoded Env, Gag, and Nef that were genetically distinct from the
proteins in the challenge virus. The
DNA vaccine induced broad-based protection without using
viral proteins to boost the immunity.