A detailed characterisation of the distribution and presentation of DNA vaccine encoded antigen

Rush, C.M., Mitchell, T.J. and Garside, P. (2010) A detailed characterisation of the distribution and presentation of DNA vaccine encoded antigen. Vaccine, 28(6), pp. 1620-1634. (doi:10.1016/j.vaccine.2009.11.014)

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Publisher's URL: http://dx.doi.org/10.1016/j.vaccine.2009.11.014

Abstract

The association between plasmid DNA distribution, the amount of Ag produced, Ag persistence and the identity and localisation of cells presenting DNA-encoded Ag all have important consequences for both quantitative and qualitative aspects of T cell responses induced by DNA vaccines. Using a variety of approaches to detect and quantify the uptake of injected DNA, and the production and presentation of DNA-encoded antigen, we report that injected DNA vaccines rapidly enter the peripheral blood from the injection site and also reach muscle-draining lymph nodes directly as free DNA. 24áh after plasmid injection, MHCII+CD11b+B220-CD11clow/- cells in the draining and distal LNs and spleen contain pDNA. Interestingly, we also observed pDNA+MHCIIlow/-CD11b+ within the bone marrow. Concomitantly, we detected Ag-containing/expressing cells at both the injection site and in draining lymph nodes. Three days after plasmid injection we detected rare pMHC+CD11c+ cells within secondary lymphoid tissue and simultaneously observed Ag-specific CD4+ T cell accumulation and blastogenesis in these tissues. Our results show that the events that determine the induction of DNA vaccine immune responses occur within days of DNA injection and that the response becomes systemic very rapidly, possibly with involvement from resident BM cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Garside, Professor Paul and Mitchell, Professor Timothy and Rush, Dr Catherine
Authors: Rush, C.M., Mitchell, T.J., and Garside, P.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Vaccine
ISSN:0264-410X
ISSN (Online):1873-2518
Published Online:23 December 2009

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
255161Investigating the Immunological Mechanisms fo DNA Vaccination Using the Adoptive Transfer of Transgenic LymphocytesTimothy MitchellWellcome Trust (WELLCOME)058006Infection Immunity and Inflammation Life Sciences