HIV-1 was among the original DNA vaccine targets and HIV DNA vaccines are n
ow in human trials. Lack of strong correlates of protective immunity makes
vaccine design difficult; however, DNA vaccines have the potential to be an
ideal vaccine and therapeutic approach against HIV-1. DNA vaccines induce
conformational -dependent antibodies, mimic live vaccines but without the p
athogenic potential, and can easily be made polyvalent. Genes which encode
important CTL and antibody epitopes can be included while those that confer
pathogenicity, virulence, antibody enhancement or represent non-conserved
epitopes can be excluded. In our hands pre-treatment of muscles with bupiva
caine or cardiotoxin did not offer any advantage over no muscle pre-treatme
nt or gene gun inoculation of skin although gene gun immunization seem to f
avour a Th2 type response. As DNA vaccine candidates we have compared vacci
nes encoding native HIV MN gp160 with Rev-independent synthetic genes encod
ing MNgp160 and MNgp120 using mammalian high expression codons. In these ex
periments the gene encoding secreted gp120 gave highest antibody neutralizi
ng titers. High and fast antibody responses could also be obtained by trans
ferring the HIV-1 MN V3 loop to the secreted HBsAg as a fusion gene vaccine
. Thus, in the case of HIV-1 MN genes encoding secreted surface glycoprotei
ns may be preferred instead of membrane bound envelopes. CTL responses were
induced in all cases. However, in order to meet the high diversity of HIV
and HLA types our approach is to include many CTL epitopes in a multivalent
minigene vaccine. We found that gene gun DNA vaccination with minimal epit
opes could induce specific CTL. Flanking sequences influenced the CTL respo
nse but was not needed. DNA vaccines encoding known and computer predicted
CTL epitopes are now being developed. (C) 1999 Elsevier Science B.V. All ri
ghts reserved.