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

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A detailed characterisation of the distribution and presentation of DNA vaccine encoded antigen. / Rush, Catherine M; Mitchell, Timothy J; Garside, Paul.

In: Vaccine, Vol. 28, No. 6, 10.02.2010, p. 1620-34.

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@article{63da79ac3b134392a743529d2266066a,
title = "A detailed characterisation of the distribution and presentation of DNA vaccine encoded antigen",
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. 24h after plasmid injection, MHCII(+)CD11b(+)B220(-)CD11c(low/-) cells in the draining and distal LNs and spleen contain pDNA. Interestingly, we also observed pDNA(+)MHCII(low/-)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.",
keywords = "Animals, Antigen Presentation, Antigens, Blood Chemical Analysis, Bone Marrow, CD4-Positive T-Lymphocytes, Dendritic Cells, Female, Lymph Nodes, Male, Mice, Mice, Inbred C57BL, Muscles, Spleen, Time Factors, Vaccines, DNA",
author = "Rush, {Catherine M} and Mitchell, {Timothy J} and Paul Garside",
note = "Copyright (c) 2009 Elsevier Ltd. All rights reserved.",
year = "2010",
month = feb,
day = "10",
doi = "10.1016/j.vaccine.2009.11.014",
language = "English",
volume = "28",
pages = "1620--34",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - A detailed characterisation of the distribution and presentation of DNA vaccine encoded antigen

AU - Rush, Catherine M

AU - Mitchell, Timothy J

AU - Garside, Paul

N1 - Copyright (c) 2009 Elsevier Ltd. All rights reserved.

PY - 2010/2/10

Y1 - 2010/2/10

N2 - 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. 24h after plasmid injection, MHCII(+)CD11b(+)B220(-)CD11c(low/-) cells in the draining and distal LNs and spleen contain pDNA. Interestingly, we also observed pDNA(+)MHCII(low/-)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.

AB - 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. 24h after plasmid injection, MHCII(+)CD11b(+)B220(-)CD11c(low/-) cells in the draining and distal LNs and spleen contain pDNA. Interestingly, we also observed pDNA(+)MHCII(low/-)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.

KW - Animals

KW - Antigen Presentation

KW - Antigens

KW - Blood Chemical Analysis

KW - Bone Marrow

KW - CD4-Positive T-Lymphocytes

KW - Dendritic Cells

KW - Female

KW - Lymph Nodes

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Muscles

KW - Spleen

KW - Time Factors

KW - Vaccines, DNA

U2 - 10.1016/j.vaccine.2009.11.014

DO - 10.1016/j.vaccine.2009.11.014

M3 - Article

C2 - 20035828

VL - 28

SP - 1620

EP - 1634

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 6

ER -