Gene inoculation generates immune responses against human immunodeficiency virus type 1.
Recently, immunization techniques in which DNA constructs are introduced directly into mammalian tissue in vivo have been developed. In theory, gene inoculation should result in the production of antigenic proteins in a natural form in the immunized host. Here we present the use of such a technique for the inoculation of mice with a human immunodeficiency virus type 1 (HIV-1) envelope DNA construct (pM160). Mice were injected intramuscularly with pM160 and were subsequently analyzed for their anti-HIV envelope immune responses. Antisera collected from inoculated animals reacted with the recombinant HIV-1 envelope in ELISA and immunoprecipitation assays. The antisera also contained antibodies that were able to neutralize HIV-1 infection and inhibit HIV-1-mediated syncytium formation in vitro. Furthermore, splenic lymphocytes derived from pM160-inoculated animals demonstrated HIV-envelope-specific proliferative responses. The gene inoculation technique mimics features of vaccination with live attenuated viruses and, therefore, may ultimately prove useful in the rapid development of safe and efficacious vaccines as it provides for production of relevant antigen in vivo without the use of infectious agents.
Wang
B
B
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Ugen
K E
KE
Srikantan
V
V
Agadjanyan
M G
MG
Dang
K
K
Refaeli
Y
Y
Sato
A I
AI
Boyer
J
J
Williams
W V
WV
Weiner
D B
DB
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015757:Genes, rev; D015756:Genes, tat; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D009132:Muscles / Q000502:physiology; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011498:Protein Precursors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D014162:Transfection / Q000276:immunology*
D015704:CD4 Antigens; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D009838:Oligodeoxyribonucleotides; D011498:Protein Precursors; D011994:Recombinant Proteins