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

Authors
  • Sylvain Cardinaud
  • Romain Bouziat
  • Pierre-Simon Rohrlich
  • Sophie Tourdot
  • Laurence Weiss
  • Pierre Langlade-Demoyen
  • Anne Burgevin
  • Susana Fiorentino
  • Peter van Endert
  • François A Lemonnier
Identifiers
DOI: 10.1097/QAD.0b013e32832fae88
Source
CdV-UPMC
License
Unknown

Abstract

To design a vaccine construct containing various but conserved HIV-1-derived epitopes and generating broad CD8 T cell responses. 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. 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. 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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