A large number of viral, parasitic, and bacterial diseases of both animal and man are resistant to or result in a poor vaccine efficacy following current immunization efforts. In many cases, these pathogens have evolved an array of recurrent molecular themes for evading, subverting, or limiting the various host defense strategies. Previous and ongoing research in this area suggests that human immunodeficiency virus type 1 (HIV-1) may have evolved and adopted an array of related strategies termed """"""""deceptive imprinting"""""""" for decoying, diverting, and functionally restricting the polyclonal nature of immune systems response. Through biophysical (shedding of viral ligands and clonal proliferation of virus), biochemical (redundant oligomeric glycoproteins, i.e. carbohydrate), deceptive imprinting (cross-reactivity and molecular mimicry) and induction of aberrant cytokine responses, the immunodominant epitopes presented in nonfunctional ways misdirect the immune system. In addition, it appears that the HIV-1 envelope interacts with normal acute phase response plasma proteins resulting in increased viral infectivity and """"""""permissiveness"""""""", which utilizes an apparently different host cell receptor(s) in primary peripheral blood mononuclear cells and macrophages cell types. The immunodominant character of the V3 loop may be part of a viral adaptation to decoy, focus, and restrict the developing immune response to V3, thus diverting the immune response away from other more conserved epitopes. To test this hypothesis, the V3 domain was masked through the novel addition of N-linked carbohydrate sequences and reduced in a net positive charge. This resulted in glycosylation, antigenic masking, retention of soluble CD4 binding, and the shift of binding and neutralizing of antibody responses to other conserved regions of the viral envelope. These results suggest an antigenic gradient of responses within which gp160 exists, and masking of the more dominant response in V3 can lead to enhanced recognition of others. Attempts are currently underway to mask other potential immunodominant decoying epitopes to focus the immune response on the broadest and most protective epitopes possible. Should specific epitiopes be identified to be protective, improved immune responses to these are being attempted through the construction of N- and O-linked glycopeptides. Preliminary evidence suggests that improved antibody binding occurs with monoclonals which have been generated using more native viral antigens.
