title: Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells.
abstract: Polyvalent mosaic HIV immunogens offer a potential solution for generating vaccines that can elicit immune responses against genetically diverse viruses. However, it is unclear whether key T cell epitopes can be processed and presented from these synthetic Ags and recognized by epitope-specific human T cells. In this study, we tested the ability of mosaic HIV immunogens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors to process and present major HIV clade B and clade C CD8 T cell epitopes in human cells. A bivalent mosaic vaccine expressing HIV Gag sequences was used to transduce PBMCs from 12 HIV-1-infected individuals from the United States and 10 HIV-1-infected individuals from South Africa; intracellular cytokine staining, together with tetramer staining, was used to assess the ability of mosaic Gag Ags to stimulate pre-existing memory responses compared with natural clade B and C vectors. Mosaic Gag Ags expressed all eight clade B epitopes tested in 12 United States subjects and all 5 clade C epitopes tested in 10 South African subjects. Overall, the magnitude of cytokine production induced by stimulation with mosaic Ags was comparable to clade B and clade C Ags tested, but the mosaic Ags elicited greater cross-clade recognition. Additionally, mosaic Ags induced HIV-specific CD4 T cell responses. Our studies demonstrate that mosaic Ags express major clade B and clade C viral T cell epitopes in human cells, as well as support the evaluation of mosaic HIV-1 vaccines in humans.
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Charlestown, MA 02129, USA.
authors.forename: Zaza M
authors.initials: ZM
authors.lastname: Ndhlovu
authors.forename: Alicja
authors.initials: A
authors.lastname: Piechocka-Trocha
authors.forename: Seanna
authors.initials: S
authors.lastname: Vine
authors.forename: Ashley
authors.initials: A
authors.lastname: McMullen
authors.forename: Kegakilwe C
authors.initials: KC
authors.lastname: Koofhethile
authors.forename: Phillip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D015683:Gene Products, gag / Q000008:administration & dosage / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D013019:South Africa; D013045:Species Specificity; D014481:United States
chemical_list: D016915:AIDS Vaccines; D015683:Gene Products, gag