Combined intra- and extracellular immunization against human immunodeficiency virus type 1 infection with a human anti-gp120 antibody.
In this study, a human CD4+ T lymphocyte line was transduced to secrete Fab fragments of a broadly neutralizing human monoclonal antibody F105 that reacts with the CD4-binding site of human immunodeficiency virus type 1 (HIV-1) envelope protein. In the transduced cells infected with HIV-1, the nascent Fab fragments bind intracellularly to the HIV-1 envelope protein and inhibit HIV-1 production. The secreted Fab fragments are able to neutralize cell-free HIV-1. In addition, the nascent Fab fragments can inhibit HIV-1 production by binding intracellularly to envelope mutants that escape neutralization by extracellular F105 antibody. The combined intra- and extracellular binding activities of the expressed Fab fragments result in the efficient blocking of cytopathic syncytium formation and infectious virus production. Thus, these antibody-producing T lymphocytes are not only resistant to HIV-1 infection but also can protect surrounding lymphocytes by secreting neutralizing antibodies. This novel strategy of combining intracellular and extracellular immunization may be useful for gene therapy of AIDS and other diseases.
Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
S Y
SY
Chen
Y
Y
Khouri
J
J
Bagley
W A
WA
Marasco
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000096:biosynthesis / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D014162:Transfection
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D017931:DNA Primers; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains