INTRACELLULAR AND EXTRACELLULAR IMMUNIZATION AGAINST HIV-1 INFECTION WITH LYMPHOCYTES TRANSDUCED WITH AN AAV VECTOR EXPRESSING A HUMAN ANTI-GP120 ANTIBODY

Recently, ae developed a novel anti-HIV-1 approach by transducing an a nti-gp120 antibody gene into lymphocytes, resulting in the resistance to HIV-1 infection by the combined intra- and extracellular binding ac tivities of the neutralizing antibody, To extend this study, we improv ed the co-expression of the heavy and light chains of the Fab105 fragm ent of the anti-gp120 antibody F105 by using an internal ribosome entr y site (IRES) sequence. The Fabl05 expression cassette was then cloned into an adeno-associated virus (AAV) shuttle vector, and encapsidated recombinant AAV-Fab105 vectors were produced. The Fab105 antibody gen e was shown to be transduced into human lymphocytes by using the recom binant AAV viruses, The transduced lymphocytes were able to produce an d secrete the Fab105 fragments, while maintaining their normal morphol ogy, growth rates, and responsiveness to mitogen stimulation, The infe ction of several primary HIV-1 patient isolates was effectively blocke d in the transduced lymphocytes. This study indicates that the combine d intra- and extracellular immunization approach may be useful for the treatment of HIV-1-infected patients.