Human immunodeficiency virus (HIV)-specific immune responses are generated with the simultaneous vaccination of a gp120-depleted, whole-killed HIV-1 immunogen with cytosine-phosphorothioate-guanine dinucleotide immunostimulatory sequences of DNA.
OBJECTIVE
We compared the effect of priming with a synthetic oligodeoxynucleotide (ODN) immunostimulatory DNA sequence followed by vaccination with human immunodeficiency virus type 1 (HIV-1) in incomplete Freund's adjuvant (IFA) or HIV-1 antigen alone to the simultaneous administration of immunostimulatory sequences (ISS) with HIV-1 in IFA.


METHODS
We examined immune function involving interferon-gamma (IFN-gamma) production, RANTES (regulated upon activation, normal T cell expressed and secreted) production, and lymphocyte proliferation, all of which appear to be augmented in HIV-1-exposed, but uninfected, individuals.


RESULTS
We demonstrate that similar levels of antigen-specific IFN-gamma were produced from lymph node cells of the animals immunized with HIV-1 antigen in IFA containing the CpG ODN 1826 (ISS; mean +/- SE = 450.8 +/- 224.3 pg/mL) and the group of animals primed with the ODN before injection with the HIV-1 in IFA (mean +/- SE = 377.7 +/- 294.8 pg/mL) or HIV-1 antigen alone (IFN-gamma = 0 pg/mL). However, the group that received the HIV-1 in IFA plus ISS mounted a stronger lymphocyte proliferation (mean net +/- SE = 29,180 +/- 1,932 cpm) compared to the group primed with the ODN before injection with HIV-1 in IFA (mean net +/- SE = 8,575 +/- 2,978 cpm). Furthermore, the group that received the HIV-1 in IFA plus ISS also mounted stronger beta-chemokine production measured as RANTES (mean +/- SE = 1,217 +/- 267.4 pg/mL) compared to the group that received the ODN before injection with HIV-1 in IFA (mean +/- SE = 129.1 +/- 48.5 pg/mL). Antibody responses from the group that received the HIV-1 in IFA plus ISS also showed a higher p24-specific response that was predominantly of the immunoglobulin G IgG2b isotype.


CONCLUSIONS
These results suggest that the simultaneous administration of the ISS in the HIV-1 in IFA emulsion may be a condidate for testing in non-human primates and in human studies as a therapeutic and preventative vaccine.
Moss
R B
RB
The Immune Response Corporation, Carlsbad, California 92008, USA. shotdoc@imnr.com
Diveley
J
J
Jensen
F C
FC
Gouveia
E
E
Carlo
D J
DJ
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018899:CpG Islands / Q000276:immunology*; D004279:DNA, Viral / Q000276:immunology*; D005620:Freund's Adjuvant / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008055:Lipids; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000276:immunology*
D016915:AIDS Vaccines; D018946:Chemokine CCL5; D004279:DNA, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008055:Lipids; D009838:Oligodeoxyribonucleotides; D019444:Vaccines, DNA; C114843:incomplete Freund's adjuvant; D007371:Interferon-gamma; D005620:Freund's Adjuvant