DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and nonhuman primates.
DNA, or genetic, inoculation mimics aspects of attenuated vaccines in that synthesis of specific foreign proteins is accomplished in the host. These proteins can be processed and presented on the relevant major histocompatibility complex (MHC) antigens and ultimately become the subject of immune surveillance. Very recently, we have described the use of the new technology to generate immune responses in mice against the human immunodeficiency virus type 1 (HIV-1) envelope using a gp160 DNA construct. Further analysis of this technology specifically in regard to HIV vaccine design is clearly important. In this report, we describe the analysis of additional HIV constructs as immunogens in both mice and report the use of this genetic immunization technology in nonhuman primates. In these studies, successful seroconversion occurs in more than 70% of the mice following the second immunization with 100 micrograms of construct DNA; three and four immunizations result in routinely 100% seroconversion of the mice. Furthermore, the same strategy has successfully seroconverted primates following their second inoculation, resulting in the generation of both antiviral and neutralizing antibodies in this animal species. These studies are the first report of which we are aware that demonstrate successful immunization of nonhuman primates through genetic vaccination technology and the first to describe genetic immunization of primates against HIV antigens. This technology has relevance for the development of safe and efficacious immunization strategies against HIV because it provides for relevant antigen production in vivo without the use of infectious agents.
Wang
B
B
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Boyer
J
J
Srikantan
V
V
Coney
L
L
Carrano
R
R
Phan
C
C
Merva
M
M
Dang
K
K
Agadjanan
M
M
Gilbert
L
L
D016915:AIDS Vaccines / Q000235:genetics*; D000818:Animals; D004279:DNA, Viral / Q000235:genetics; D015694:Gene Products, rev / Q000276:immunology; D015696:Gene Products, tat / Q000276:immunology; D005814:Genes, Viral; D015752:Genes, env; D016355:Genes, pX; D015757:Genes, rev; D015483:HIV Antibodies / Q000096:biosynthesis; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D004279:DNA, Viral; D015694:Gene Products, rev; D015696:Gene Products, tat; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus