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315 Human Monoclonal Antibodies (mAbs) Generated from Cells of Clade A-Infected Individuals
S. Zolla-Pazner*1,2, B. Volsky1, C. Williams1, K. Revesz2, S. Cohen1, P. Nyambi1, W. J. Honnen3, C. Krachmarov3, A. Pinter3, and M. K. Gorny1
1New York Univ. Sch. of Med., USA; 2Veterans Affairs Med. Ctr., New York, NY, USA; and 3Publ. Hlth. Res. Inst., New York, NY, USA
Background: Most studies of the antigenic nature of HIV envelope proteins have been performed with glycoproteins from clade B. Similarly, detailed immunologic studies of the epitopes of the HIV envelope have focused on responses by clade B-infected individuals. Design of a vaccine useful on the global stage requires identification of antigenic structures that induce immunity to all clades. mAbs derived from non-B-infected subjects will help to define the immune response to diverse HIV strains.
Methods: Human mAbs were produced from PBMCs from subjects infected in Africa with HIV. Infecting clades were identified with the heteroduplex mobility assay. Binding of mAbs to intact virions was tested by capture ELISA, and neutralizing activity was determined by flow-cytometric measurement of GHOST cells infected with primary isolates and by a luciferase assay using pseudoviruses.
Results: Three human mAbs were derived from clade A-infected individuals: (1) An anti-V3 mAb was selected with a V3MJR-CSF-MuLV gp70 fusion protein (V3-FP); this mAb bound best to intact, native virions of clades A, B, D, and F. Significant neutralizing activity was observed with <25 mug/ml against 2/2 clade A and 2/3 clade B primary isolates and with <10 mug/ml against pseudoviruses SF162 and JR-FL. (2) An anti-gp41 mAb was directed to the cluster I epitope (aa 579(604), could bind to all intact virions from all clades tested, but had no neutralizing activity. (3) A mAb was also selected that was specific for gp70 of MuLV, the protein with which the V3-FP was constructed.
Conclusions: This is the first description of human mAbs derived from clade A-infected individuals. One of these, a mAb selected with a V3-FP (which retains V3 conformational epitopes) displays cross-clade neutralizing activity. The gp41 mAb described can bind to clades A, B, C, E, and F virions but does not neutralize.
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