Accession Number : ADA314736

Title :   Support of Study Entitled; Conformationally Restricted Synthetic AIDS Vaccine.

Descriptive Note : Annual rept. 1 Jul 95-30 Jun 96,

Corporate Author : SCRIPPS RESEARCH INST LA JOLLA CA

Personal Author(s) : Satterthwait, Arnold C.

PDF Url : ADA314736

Report Date : JUL 1996

Pagination or Media Count : 78

Abstract : HIV-1 initiates infection by attaching itself to CD4 on immune system cells. Two reagents, IgG1b12 and tetrameric CD4-IgG2, bind the envelop glycoprotein, gp12O, on HIV-1, block this reaction and prevent infection. We have focused our research on the identification and mimicry of epitopes recognized- by these reagents for use as a vaccine. We present 4 reports. A constrained DPE peptide loop based on Asp368ProGlu37O from the gp12O sequence has been used to isolate a neutralizing MAb similar to IgGlbl2. A 3-D structure prediction for the Vl/V2 domain on gp12O which plays a role in the neutralization of HIV-1 by 1gG1b12 is presented and provides a basis for the design of constrained peptide vaccines. Both phage-peptide and synthetic peptide libraries have been extensively screened with Fab 12 and sCD4. Synthetic peptides characterized by Asp, Glu and rich in trptophans have been identified that block sCD4/gp120 and Fab 12/gp12O binding with IC5O = 10-100 uN. Finally, the DPE loop has been ligated to a 'universal' T-cell epitope to yield a pure, well characterized four-branched loop-NAPS that is immunogenic in outbred mice and stimulates antibodies that bind recombinant gp120 IlIB.

Descriptors :   *INFECTIOUS DISEASES, *HUMAN IMMUNODEFICIENCY VIRUSES, *VACCINES, *ACQUIRED IMMUNE DEFICIENCY SYNDROME, PEPTIDES, NEUTRALIZATION, GLYCOPROTEINS, IDENTIFICATION, LIMITATIONS, CHEMICAL AGENTS, ANTIBODIES, MICE, IMMUNITY, CELLS(BIOLOGY), LOOPS, LIBRARIES.

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE