Design of a HIV-1-derived HLA-B07.02-restricted polyepitope construct.

Abstract : OBJECTIVE: To design a vaccine construct containing various but conserved HIV-1-derived epitopes and generating broad CD8 T cell responses. METHODS: HLA-B7 transgenic H-2KD KO transgenic mice were used to identify potential new HLA-B07.02-restricted HIV-1-derived epitopes. Immunological recognition of these epitopes was confirmed by IFN-gamma ELISpot assays with PBMCs from HLA-B*0702 HIV-1-infected individuals. For these peptides as well as others previously identified, the capacity to induce cross-reactive responses against their frequent allelic variants was evaluated in the mouse model. A set of epitopes inducing strong T cell responses against various and conserved regions of HIV-1 was selected. A DNA vaccine was designed to express them as a unique antigen with or without a three amino acid ARY extension flanking each epitope. The spectrum of CD8 T responses generated by polyepitope constructs was tested in HLA-B7 transgenic mice. RESULTS: Five new epitopes were identified in accessory and regulatory HIV-1 proteins. Twelve HLA-B07.02-restricted epitopes were selected on the basis of their structural conservation and cross-reactive immunogenicity. The ARY N-terminal extension flanking each epitope markedly increases their affinity for TAP and the use of this flanking extension in polyepitope vaccine has a sizable advantage to induce CD8 T cell cytotoxic responses in mice following DNA immunization. CONCLUSION: The HLA-B7 mouse model allows to rapidly identify various HIV-1-derived epitopes of vaccine interest. Grouped in a polyepitope construct designed to increase their processing, this vaccine may be suitable for inducing multiple and relevant HIV-1-specific CTL responses in humans.
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AIDS, Lippincott, Williams & Wilkins, 2009, 23 (15), pp.1945-54. 〈10.1097/QAD.0b013e32832fae88〉
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Soumis le : mercredi 19 mai 2010 - 09:54:44
Dernière modification le : lundi 9 juillet 2018 - 13:12:02

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Sylvain Cardinaud, Romain Bouziat, Pierre-Simon Rohrlich, Sophie Tourdot, Laurence Weiss, et al.. Design of a HIV-1-derived HLA-B07.02-restricted polyepitope construct.. AIDS, Lippincott, Williams & Wilkins, 2009, 23 (15), pp.1945-54. 〈10.1097/QAD.0b013e32832fae88〉. 〈inserm-00484766〉

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