Development of Immunoregulatory Peptides for AIDS

Morrow, William

Abstract

The need to develop effective immunoregulatory ar anti-viral reagents that will control HIV infection is paramount. In the course of our studies of the CD4 attachment site on the HIV envelope we have identified a synthetic peptide with properties that suggest it may be a strong candidate therapeutic agent. The peptide (termed A25D) represents an 18 amino acid sequence from the putative CD4 attachment site on gpl2O and biophysical comparisons suggest that it contains both B and T cell epitopes. A25D blocks HIV transmission in vitro as determined in a standard syncytial formation assay, however studies performed on HIV-infected individuals indicate that both B and T cell responses to the peptide are minimal. These findings suggest that although A25D may represent a critical epitope on the HIV binding site capable of inducing group-specific neutralization, this potential is not realized in most individuals. We attribute this finding to the fact that the highly immunodominant regions of the envelope establish a clonal dominance and suppress effective responses to the attachment site. For Phase I of this proposal we describe a series of experiments which will examine the potential utility of A25D and related peptides to be used as agents to promote active anti-HIV immunity. Specifically, we will test the ability of the material to induce anti-gpl2O responses in mice and rabbits. Furthermore, we will use A25D and related synthetic and recombinant peptides to screen and characterize the sera of HIV-infected individuals and SIV-infected macaques for virus neutralizing antibodies. Finally, as a prelude to Phase II studies in which we propose to use the peptides as boosting reagents for HIV infection,, we will determine the ability to stimulating virion production, by stimulating infected lymphocytes.