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Peptides 2007 Mar;28(3):496-504

Antibodies against a multiple-peptide conjugate comprising chemically modified human immunodeficiency virus type-1 functional Tat peptides inhibit infection.

Devadas K, Boykins RA, Hewlett IK, Wood OL, Clouse KA, Yamada KM, Dhawan S

Dhawan S (reprint author), US FDA, Immunopathogenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, 140 Rockville Pike,HFM 315, Rockville, MD 20852 USA US FDA, Immunopathogenesis Sect, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA Cell Biol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA

Abstract

We demonstrated recently that selective side-chain modification of functional cysteine-rich (Tat(21-40)) and arginine-rich (Tat(53-68)) domains of the HIV-1 Tat protein blocks pathogenic activities of these peptides while retaining their immunological characteristics. In the present study, we have synthesized a multiple-peptide conjugate system comprising modified Tat(21-40) and Tat(53-68) peptides (HIV-1-Tat-MPC). Immunization of mice with this highly homogeneous 10.7kDa HIV-1-Tat-MPC synthetic construct induced an effective immune response in mice. The antibodies generated against HIV-1-Tat-MPC efficiently suppressed Tat-induced viral replication and significantly reduced HIV-associated cytopathic effects in human monocytes. These results indicate that epitope-specific antibodies directed against functional sites of Tat protein using non-pathogenic peptides inhibit HIV pathogenesis. The HIV-1-Tat-MPC, therefore, has potential for the development of a safe, effective, and economical therapeutic vaccine to reduce the progression of HIV infection.


Category: Journal Article
PubMed ID: #17188401
Includes FDA Authors from Scientific Area(s): Biologics, Drugs
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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