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Session 66 Poster Presentations New Antiretrovirals Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall A

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Biological and Biochemical Characterization of a Highly Polymerized CD4-Ig Fusion Protein that Mediates Efficient Antibody Dependent Cell Mediated Cytotoxicity Against HIV-infected Cells
N. S. Gupta*¹, T. D.Steenbeke², D. Van Ryk², P. Sun³, S. Radaev³, P. Schuck⁴, D. Mavilio², S. Kottilil², M. A. Chaikin², P. Khazanie², R. Rabin⁵, C. Cicala², J. Arthos², A. S. Fauci^2
1Howard Hughes Med Inst (HHMI)-NIH Res Scholars Prgm, Bethesda, MD; ²Lab of Immunoregulation/NIAID/NIH, Bethesda, MD; ³Natl Inst of Allergy and Infectious Diseases, NIH, Bethesda, MD; ⁴Office of Dietary Suppl (OD), NIAID, NIH, Bethesda, MD; and ⁵Ctr for Biologics Eval and Res, FDA, Bethesda, MD

Background: A principal challenge in the development of an effective HIV vaccine is the elicitation of high titer neutralizing antibodies directed against the viral envelope protein gp120/41.
Methods: Effective antibody responses rely upon both F(ab)2 which confers antigen specificity and the Fc domain which mediates antibody effector functions. The potential of effector responses to contribute to the antiviral activity of potent neutralizing antibodies in vivo is unclear. Effector responses are triggered by the crosslinking of Fc gamma receptors on both APCs and NK cells.
Results: In this study, we characterized the effector activity of a dodecameric CD4-Ig fusion protein that efficiently neutralizes primary isolates of HIV. This recombinant Ig fusion protein binds multiple Fc gamma RIIIs on primary NK cells. Crosslinking by this protein results in signal transduction through Fc gamma RIII that elicits a potent antibody directed cell-mediated cytotoxicity of HIV-infected target cells.
Conclusions: These observations provide insight into the design and development of therapeutic agents and vaccines directed against HIV.

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