Effect of different promoters on immune responses elicited by HIV-1 gag/env multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina.
pCMV-NL(Deltapol) and pAKV-NL(Deltapol) expressed human immunodeficiency virus type 1 (HIV-1) gag and env under the regulation of the human cytomegalovirus (CMV) immediate-early (IE) promoter/enhancer and the endogenous AKV murine leukemia viral long terminal repeat (LTR), respectively. Analysis of the immune responses elicited by direct DNA injection of pCMV-NL(Deltapol) and pAKV-NL(Deltapol) in macaques indicated that generation of the humoral and T-cell proliferative responses correlated directly with the promoter strength of the vaccine DNAs. In Macaca mulatta, pCMV-NL(Deltapol) generated stronger humoral responses and T-cell proliferative responses to Gag and Env using less DNA and fewer number of injections than pAKV-NL(Deltapol). Similarly, in Macaca nemestrina pCMV-NL(Deltapol) elicited high humoral responses, which persisted long-term and were boostable. Injection of large amounts of pAKV-NL(Deltapol), in general, failed to produce antibody levels comparable to pCMV-NL(Deltapol). However, injection of a control animal with large amounts of vector DNA produced a generalized enzyme-linked immunosorbent assay (ELISA) reactivity to HIV-1. The results indicated that generation of high immune responses to HIV-1 cannot be achieved by increasing the vaccine DNA dose and may require high protein expression from the DNA by including a strong promoter or by the use of other boosting agents. Furthermore, safety concerns may arise with increasing the DNA dose that could need additional investigation.
Galvin
T A
TA
Laboratory of Retrovirus Research, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892, USA.
Muller
J
J
Khan
A S
AS
D016475:3T3 Cells; D016915:AIDS Vaccines / Q000276:immunology*; D000406:AKR murine leukemia virus / Q000235:genetics*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D017930:Genes, Reporter; D005814:Genes, Viral; D015752:Genes, env; D015750:Genes, gag; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000096:biosynthesis / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000096:biosynthesis / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008254:Macaca nemestrina; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012208:Rhabdomyosarcoma / Q000473:pathology; D012449:Safety; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D020079:Terminal Repeat Sequences; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*; D014709:Vero Cells
D016915:AIDS Vaccines; D000956:Antigens, Viral; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C044582:immediate-early proteins, cytomegalovirus; D015500:Chloramphenicol O-Acetyltransferase