174 The C5 region of gp120: A therapeutic vaccine target?

Abstract

HIV infection does not always lead to disease as demonstrated by very long term non progressors and chimpanzees. The difference between progressors and non progressors is the degree of non specific pan activation of the immune system which is absent in the latter. The cause of this genetically restricted pan activation has yet to be confirmed. However, recognized causes such as hypervariability and superantigen stimulation are not relevant to HIV. Another potential cause is allogeneic stimulation. HIV has several regions of homology to HLA class 1 and 11. We have reported that C5 is structurally very similar in that it and no other region bind specific class 1 and class 2 peptides. Moreover, when the region is itself presented as a peptide in context of self HLA it is recognized as an alloepitope. As such it would be closest to a self peptide in HLA-27 and most pronounced as an alloepitope in HLA-8. This is consistent with HLA-27 being associated with slow progression and HLA-8 with fast progression. Furthermore, chimps have very restricted HLA types similar to HLA-27/57. Several large studies have reported the presence of anti-bodies to C5 in non progressors but these observations have been discounted as the antibodies are non neutralizing. Here, we propose that if these antibodies are preventing the C5 region from inducing the activation that drives AIDS, then a therapeutic vaccine aimed at inducing this response following immune normalization with HAART may allow some patients to convert to non progressors and no longer be dependant on HAART therapy. As this region is so highly conserved amongst all viable isolates it may well be a good candidate for a prophylactic vaccine as sterilising immunity is clearly not necessary in order to prevent progression to AIDS. Therapeutic non-neutralising vaccines need not be limited to HIV!