COMBINED INTRACELLULAR 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 secr ete Fab fragments of a broadly neutralizing human monoclonal antibody F105 that reacts with the CD4-binding site of human immunodeficiency v irus 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 fra gments are able to neutralize cell-free HIV-1. In addition, the nascen t Fab fragments can inhibit HIV-1 production by binding intracellularl y 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 cytop athic syncytium formation and infectious virus production. Thus, these antibody-producing T lymphocytes are not only resistant to HIV-1 infe ction but also can protect surrounding lymphocytes by secreting neutra lizing antibodies. This novel strategy of combining intracellular and extracellular immunization may be useful for gene therapy of AIDS and other diseases.