Preclinical studies on immunogenicity of the HIV-1 p17-based synthetic peptide AT20-KLH
✍ Scribed by Simona Fiorentini; Elena Marini; Luisa Bozzo; Laura Trainini; Lamiaa Saadoune; Manuela Avolio; Angela Pontillo; Carlo Bonfanti; Paolo Sarmientos; Arnaldo Caruso
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2004
- Tongue
- English
- Weight
- 288 KB
- Volume
- 76
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
Abstract
Several studies have suggested that HIV‐1 p17 matrix protein may play an important role in AIDS pathogenesis, since anti‐p17 antibodies represent a serological marker of disease progression during HIV‐1 infection both in adults and children. Moreover, it has been recently reported that the viral protein is capable of significantly increasing the proliferation of preactivated T lymphocytes and the release of proinflammatory cytokines. Recombinant HIV‐1 p17 also has induced an increased rate of HIV‐1 replication in vitro. All p17 biological activities are exerted after its binding to a specific cellular receptor expressed on activated T lymphocytes. The functional p17 epitope involved in receptor binding was found to be located at the NH~2~‐terminal region of the viral protein. Immunization of C57BL/6 mice with a 20 amino acid synthetic peptide representative of the HIV‐1 p17 functional region (AT20) coupled to the carrier protein keyhole limpet hemocyanin (KLH) and given in Freund's incomplete adjuvant, resulted in the development of p17‐neutralizing antibodies capable of blocking p17/p17 receptor interaction, and consequently, all biological activities of the viral protein. Moreover, it was possible to skew the humoral response induced by priming mice with AT20‐KLH toward cell‐mediated immune responses, boosting animals with p17. Our findings may provide a new strategy to develop a synthetic AIDS vaccine based on a potentially effective and safe subunit vaccine against the HIV‐1 cytokine‐like matrix protein p17. Preclinical immunogenicity data for AT20‐KLH provide the basis for evaluation of the peptide‐basedvaccine, alone and in combination with p17 or p17 DNA vaccines, in Phase I clinical trials. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004