Of critical concern to the National HIV Vaccine Program is the design of HIV immunogens which can elicit broadly neutralizing antibodies (group-specific) rather than neutralizing antibodies of narrow specificity (type-specific). Current evidence indicates that group-specific antibodies recognize conformational epitopes which are dependent in an unknown manner on glycosylation of gpl20. This study is designed to probe the effect of N-glycosylation of the HIV env-proteins on these conformational epitopes and determine whether there are critical glycosyl residues involved in the maintenance of native conformation of these group-specific epitopes. This study will analyze the effects of inhibition at various steps of N-glycosylation processing (i.e.-global effect) and the HIV glycosylation patterns dependent on the producer cell (i.e.-site-specific effect) as a function of neutralization by conformation dependent neutralizing monoclonal antibodies. Differential peptide mapping and enzymatic analysis of glycosyl units will be used to target specific glycosylation sites (Asn-X-Ser/Thr) for subsequent microsequence analysis of site-specific carbohydrate structure.
| Mitchell, W M; Ding, L; Gabriel, J (1998) Inactivation of a common epitope responsible for the induction of antibody-dependent enhancement of HIV. AIDS 12:147-56 |
| Gabriel, J L; Mitchell, W M (1996) Functional design of potential inhibitors of human immunodeficiency virus (HIV) binding to CD4+ target cells: a molecular model of gp120 predicts ligand binding. Drug Des Discov 14:103-14 |
| Mitchell, W M; Rosenbloom, S T; Gabriel, J (1995) Induction of mucosal anti-HIV antibodies by facilitated transfection of airway epithelium with lipospermine/DNA complexes. Immunotechnology 1:211-9 |
