title: Modified anthrax fusion proteins deliver HIV antigens through MHC Class I and II pathways.
abstract: T cell-based HIV vaccine candidates have focused on eliciting both CD4- and CD8-mediated responses. One challenge in vaccine development is the successful introduction and presentation of exogenous antigen to elicit an immune response. Modified bacterial toxins have been studied extensively as intracellular delivery agents because of their unique capability to translocate antigen across the cell membrane without affecting cell viability. Modified anthrax toxin lethal factor (LFn) fusion protein is able to effectively induce anti-HIV cytotoxic T lymphocytes in the absence of protective antigen (PA) and is being evaluated as a vaccine candidate. Here we describe, for the first time, the processing and presentation of LFn fusion proteins by the MHC Class II pathway. The ability of LFn--HIV to induce both CD8- and CD4-mediated responses may have relevance in current approaches to vaccine design. Furthermore, the translocation and presentation of antigens occurs in the absence of PA, which proposes a modified molecular mechanism of antigen presentation by the anthrax toxin model. Additionally, we found that LFn--HIV is specific and sensitive in detecting HIV-specific CD4(+) and CD8(+) T cell responses in T cell assays, further broadening the value of this antigen delivery system as a useful immunologic tool.
authors.affiliation: California Department of Health Services, 850 Marina Bay Parkway, VRDL, Richmond, CA 94804, USA. kmcevers@dhs.ca.gov
authors.forename: K
authors.initials: K
authors.lastname: McEvers
authors.forename: M
authors.initials: M
authors.lastname: Elrefaei
authors.forename: P
authors.initials: P
authors.lastname: Norris
authors.forename: S
authors.initials: S
authors.lastname: Deeks
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: H
authors.initials: H
authors.lastname: Cao
mesh_terms: D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D015488:HIV Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000187:drug effects* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; C030325:anthrax toxin