Intra- and Extracellular Immunization Against HIV-1 Infection with Lymphocytes Transduced with an AAV Vector Expressing a Human Anti-gp120 Antibody

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Abstract
Recently, we developed a novel anti-HIV-1 approach by transducing an anti-gp120 antibody gene into lymphocytes, resulting in the resistance to HIV-1 infection by the combined intra- and extracellular binding activities of the neutralizing antibody. To extend this study, we improved the co-expression of the heavy and light chains of the Fab105 fragment of the anti-gp120 antibody F105 by using an internal ribosome entry site (IRES) sequence. The Fab105 expression cassette was then cloned into an adeno-associated virus (AAV) shuttle vector, and encapsidated recombinant AAV-Fab105 vectors were produced. The Fab105 antibody gene was shown to be transduced into human lymphocytes by using the recombinant AAV viruses. The transduced lymphocytes were able to produce and secrete the Fab105 fragments, while maintaining their normal morphology, growth rates, and responsiveness to mitogen stimulation. The infection of several primary HIV-1 patient isolates was effectively blocked in the transduced lymphocytes. This study indicates that the combined intra- and extracellular immunization approach may be useful for the treatment of HIV-1-infected patients. A human anti-HIV-1 gp120 antibody gene can be transduced into human lymphocytes by using an adeno-associated virus (AAV) vector system. The infection of several primary HIV-1 patient isolates was effectively blocked in the transduced lymphocytes by the combined intra- and extracellular binding activities of the neutralizing antibody. This study indicates that this novel combined intra- and extracellular immunization approach may be useful for the treatment of HIV-1-infected patients.