A large number of viral, parasitic, andbacterial diseases of both animal and man areresistant to or result in a poor vaccine efficacyfollowing current immunization efforts. In manycases, these pathogens have evolved an array ofrecurrent molecular themes for evading,subverting, or limiting the various host defensestrategies. Previous and ongoing research in thisarea suggests that human immunodeficiency virustype 1 (HIV-1) may have evolved and adopted anarray of related strategies termed """"""""deceptiveimprinting"""""""" for decoying, diverting, andfunctionally restricting the polyclonal nature ofimmune systems response. Through biophysical(shedding of viral ligands and clonalproliferation of virus), biochemical (redundantoligomeric glycoproteins, i.e. carbohydrate),deceptive imprinting (cross-reactivity andmolecular mimicry) and induction of aberrantcytokine responses, the immunodominant epitopespresented in nonfunctional ways misdirect theimmune system. In addition, it appears that theHIV-1 envelope interacts with normal acute phaseresponse plasma proteins resulting in increasedviral infectivity and """"""""permissiveness"""""""",which utilizes an apparently different host cellreceptor(s) in primary peripheral bloodmononuclear cells and macrophages cell types. Theimmunodominant character of the V3 loop may bepart of a viral adaptation to decoy, focus, andrestrict the developing immune response to V3,thus diverting the immune response away from othermore conserved epitopes. To test this hypothesis,the V3 domain was masked through the noveladdition of N-linked carbohydrate sequences andreduced in a net positive charge. This resulted inglycosylation, antigenic masking, retention ofsoluble CD4 binding, and the shift of binding andneutralizing of antibody responses to otherconserved regions of the viral envelope. Theseresults suggest an antigenic gradient of responseswithin which gp160 exists, and masking of the moredominant response in V3 can lead to enhancedrecognition of others. Attempts are currentlyunderway to mask other potential immunodominantdecoying epitopes to focus the immune response onthe broadest and most protective epitopespossible. Should specific epitiopes be identifiedto be protective, improved immune responses tothese are being attempted through the constructionof N- and O-linked glycopeptides. Preliminaryevidence suggests that improved antibody bindingoccurs with monoclonals which have been generatedusing more native viral antigens.
