Viral envelopes biochemical, biophysical, and antigenic characteristics and dynamics, such as spontaneous shedding into distinct antigenic forms could have immune delaying, dysregulating and decoying properties. The presence of immunodominant epitopes such as the V3 and gp41 region(s) (which may serve to act as an immunological decoy, and raise non- functional, blocking, or enhancing antibodies) coupled to antigenic variation are critical biochemical/physical and immunological roadblocks to developing an effective acquired immunodeficiency syndrome vaccine. It appears that human immunodeficiency virus type 1 is capable of avoiding V3-specific neutralizing antibody by presenting a conformationally less related molecule to the immune system than appears on the virus particle. In addition, it appears that there are many antibodies directed at the gp120/40 which are functionless and demonstrate an array of affinities. It also appears that global molecular properties contribute readily to escape from most of these antibodies. A novel approach, however, to immunologically mask these immunodominant decoying epitopes has been developed from previous Laboratory of Tumor Cell Biology work and is being tested. The introduction of N-linked carbohydrate sites and a reduction of charged amino acids in the epitope of interest appears to refocus the immune response to other antigenic sites, thus changing qualitatatively and functionally the humoral response. This approach may have useful applications to this viral disease as well as other pathogens utilizing this immunopathogenic strategy.
