title: Alphavirus replicon particles acting as adjuvants promote CD8+ T cell responses to co-delivered antigen.
abstract: Alphavirus replicon particles induce strong antibody and CD8+ T cell responses to expressed antigens in numerous experimental systems. We have recently demonstrated that Venezuelan equine encephalitis virus replicon particles (VRP) possess adjuvant activity for systemic and mucosal antibody responses. In this report, we demonstrate that VRP induced an increased and balanced serum IgG subtype response to co-delivered antigen, with simultaneous induction of antigen-specific IgG1 and IgG2a antibodies, and increased both systemic and mucosal antigen-specific CD8+ T cell responses, as measured by an IFN-gamma ELISPOT assay. Additionally, VRP further increased antigen-specific T cell immunity in an additive fashion following co-delivery with the TLR ligand, CpG DNA. VRP infection led to recruitment of CD8+ T cells into the mucosal compartment, possibly utilizing the mucosal homing receptor, as this integrin was upregulated on CD8+ T cells in the draining lymph node of VRP-infected animals, where VRP-infected dendritic cells reside. This newly recognized ability of VRP to mediate increased T cell response towards co-delivered antigen provides the potential to both define the molecular basis of alphavirus-induced immunity, and improve alphavirus-based vaccines.
authors.affiliation: Department of Microbiology and Immunology, Carolina Vaccine Institute, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Thompson
authors.forename: Alan C
authors.initials: AC
authors.lastname: Whitmore
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
authors.forename: Robert E
authors.initials: RE
authors.lastname: Johnston
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D004347:Drug Interactions; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D016023:Integrins / Q000032:analysis; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D016023:Integrins; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma; D010047:Ovalbumin