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The Science Seminar Series: April 21, 2005
Characterization of humoral immune responses to recombinant HIV-1 gp120 genetically linked to human CD4 and a CD4 mimetic
David Onyabe, Ph.D.
Aereas Global Tuberculosis Foundation
Rockville, MD
Room 1011 Biology/Chemistry BuildingTime: 4:00 -5:00pm
Immunogens that elicit high-titer broadly neutralizing antibodies (Abs) against Human immunodeficiency virus type-1 (HIV-1) remain elusive. During entry of this virus into host cells, the 120 kDa envelope glycoprotein (gp120) attaches to cell-surface receptor CD4, resulting in conformational rearrangements that expose conserved neutralizing epitopes. It has been proposed that HIV-1 Env immunogens that display CD4-induced (CD4i) epitopes bear the antigenic capacity to induce broadly neutralizing Abs. In this study we characterized the humoral responses induced by HIV-1BaL gp120 genetically fused to: (1) the D1D2 domain of human CD4 (designated FLSCR/T); and (2) a scorpion toxin-derived CD4 mimetic (designated gp120-M9) in BALB/c mice. Only antisera from mice vaccinated with FLSCR/T effected broad neutralization of primary R5- and X4-tropic HIV-1 isolates, whereas anti-gp120-M9 sera did not reduce the infectivity of any HIV-1 strains tested. Moreover, FLSCR/T but not gp120-M9 induced antibodies that competed with the binding of CD4i epitope-specific neutralizing monoclonal antibody (mAb) X5 to soluble FLSCR/T. The possibility that some of the neutralizing activity is due to Ab against the CD4 component of FLSCR/T was not ruled out. It is not clear why gp120-M9 failed to induce neutralizing antibodies nor antibodies to CD4i epitopes recognized by the panel of mAbs tested. Nonetheless, data are shown indicating that gp120-M9 more than FLSCR/T induced serum IgG responses focused to epitopes present on non-denatured gp120.