Multideterminant peptides that elicit helper T-lymphocyte cytotoxic T-lymphocyte and neutralizing antibody responses against HIV-1

US6294322A · kind A · utility

Assignee

• The United States of America, as represented by the Department of Health and Human Services · US

Inventors

• Jay A. Berzofsky · Bethesda, US
• Jeffrey D. Ahlers · Winterville, US
• C. David Pendleton · Bethesda, US
• Peter L. Nara · Frederick, US
• Mutsunori Shirai · Rockville, US

Key dates

• Filing date: May 14, 1993
• Grant date: Sep 25, 2001
• Expiry date: May 14, 2013

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02A50/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Peptide constructs comprised of multideterminant T helper peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52-73% of HIV positive, flu positive patients (cluster peptides), were co-linearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB and also shown to contain a dominant CTL epitope. Cognate help for peptide 18 antibody was elicited following a single immunization in all strains of mice which had previously responded to a T cell epitope encompassed by the peptides. In two strains of mice, the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, much higher antibody titers for 90% neutralization in the range of 1:1000 to 1:16,000 were achieved. Spleen cells from mice of three distinct MHC haplotypes sharing the D.sup.d class I MHC molecule but with different class II molecules, immunized with the compound peptides, exhibited enhanced gp160-specific CTL activity.