Journal
VACCINE
Volume 26, Issue 33, Pages 4267-4275Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2008.05.046
Keywords
viral adjuvants; viral vaccine vectors; cell-mediated immunity
Categories
Funding
- National Institutes of Allergy and Infectious Diseases/National Institutes of Health [P01-AI046023, R01-AI051990, U01A1070976, T32-AI007419]
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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. (C) 2008 Elsevier Ltd. All rights reserved.
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