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© Research
Publication : AIDS (London, England)

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in AIDS (London, England) - 24 Sep 2009

Cardinaud S, Bouziat R, Rohrlich PS, Tourdot S, Weiss L, Langlade-Demoyen P, Burgevin A, Fiorentino S, van Endert P, Lemonnier FA

Link to Pubmed [PMID] – 19644347

AIDS 2009 Sep;23(15):1945-54

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.

http://www.ncbi.nlm.nih.gov/pubmed/19644347