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Prime-boost with alternating DNA vaccines designed to engage different antigen presentation pathways generates high frequencies of peptide-specific CD8+ T cells

Prime-boost with alternating DNA vaccines designed to engage different antigen presentation pathways generates high frequencies of peptide-specific CD8+ T cells
Prime-boost with alternating DNA vaccines designed to engage different antigen presentation pathways generates high frequencies of peptide-specific CD8+ T cells
The route for presentation of Ag to CD8+ or CD4+ T cells following DNA vaccination is critical for determining outcome, but the pathways involved are unclear. In this study, we compare two different DNA vaccine designs aimed to elicit CD8+ T cell responses against a specific peptide-epitope either by direct- or cross-presentation. Each carries sequences from tetanus toxin (TT) to provide essential CD4+ T cell help. In the first already proven design, the peptide-epitope is fused to the N-terminal domain of fragment C from TT. This appears to act mainly by cross-presentation. In the second design, the peptide-epitope is encoded by a minigene, with induction of Th responses mediated by coexpression of a hybrid invariant chain molecule, incorporating a single determinant from TT (p30) in exchange for class II-associated invariant chain peptide. This design appears to act mainly via direct presentation from transfected APCs. Both vaccines mediated Th-dependent priming of CD8+ T cells in mice, but the kinetics and level of the responses differed markedly, consistent with engagement of distinct pathways of Ag presentation. Importantly, the vaccines could be combined in an alternating prime-boost regime, in either order, generating substantially expanded memory CD8+ T cells, with potent effector function. Taken together, these results demonstrate that vaccination protocols involving different modes of Ag presentation at prime and boost can significantly improve the effectiveness of immunization.
presenting cells, cross-presentation, cell responses, sequence, cd8-t-cell memory, outcome, single, dendritic cells, dna, invariant chain peptide, plasmid dna, invariant chain, responses, tumor-antigen, peptide, protocol, pathway, antigen, induction, vaccination, antigen presentation, vaccines, cd4-t-cell help, cells, dna vaccines, genetic exchange, t cells, pathways, fragment c, cell, potent, t-cells, repair, immunization, time, t-cell, in-vivo, vaccine
0022-1767
6626-6633
Radcliffe, Joanna N.
95bba459-28f5-46d5-b1f1-8e077f115e52
Roddick, Joanne S.
dddd0a9c-ef7a-4cb4-810d-8927ff1ce76f
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Radcliffe, Joanna N.
95bba459-28f5-46d5-b1f1-8e077f115e52
Roddick, Joanne S.
dddd0a9c-ef7a-4cb4-810d-8927ff1ce76f
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de

Radcliffe, Joanna N., Roddick, Joanne S., Friedmann, Peter S., Stevenson, Freda K. and Thirdborough, Stephen M. (2006) Prime-boost with alternating DNA vaccines designed to engage different antigen presentation pathways generates high frequencies of peptide-specific CD8+ T cells. The Journal of Immunology, 177 (10), 6626-6633.

Record type: Article

Abstract

The route for presentation of Ag to CD8+ or CD4+ T cells following DNA vaccination is critical for determining outcome, but the pathways involved are unclear. In this study, we compare two different DNA vaccine designs aimed to elicit CD8+ T cell responses against a specific peptide-epitope either by direct- or cross-presentation. Each carries sequences from tetanus toxin (TT) to provide essential CD4+ T cell help. In the first already proven design, the peptide-epitope is fused to the N-terminal domain of fragment C from TT. This appears to act mainly by cross-presentation. In the second design, the peptide-epitope is encoded by a minigene, with induction of Th responses mediated by coexpression of a hybrid invariant chain molecule, incorporating a single determinant from TT (p30) in exchange for class II-associated invariant chain peptide. This design appears to act mainly via direct presentation from transfected APCs. Both vaccines mediated Th-dependent priming of CD8+ T cells in mice, but the kinetics and level of the responses differed markedly, consistent with engagement of distinct pathways of Ag presentation. Importantly, the vaccines could be combined in an alternating prime-boost regime, in either order, generating substantially expanded memory CD8+ T cells, with potent effector function. Taken together, these results demonstrate that vaccination protocols involving different modes of Ag presentation at prime and boost can significantly improve the effectiveness of immunization.

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More information

Published date: 15 November 2006
Keywords: presenting cells, cross-presentation, cell responses, sequence, cd8-t-cell memory, outcome, single, dendritic cells, dna, invariant chain peptide, plasmid dna, invariant chain, responses, tumor-antigen, peptide, protocol, pathway, antigen, induction, vaccination, antigen presentation, vaccines, cd4-t-cell help, cells, dna vaccines, genetic exchange, t cells, pathways, fragment c, cell, potent, t-cells, repair, immunization, time, t-cell, in-vivo, vaccine

Identifiers

Local EPrints ID: 59394
URI: http://eprints.soton.ac.uk/id/eprint/59394
ISSN: 0022-1767
PURE UUID: 1a7ff193-ec97-4021-90e5-c7b1bfad4665
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

Catalogue record

Date deposited: 03 Sep 2008
Last modified: 05 Nov 2019 02:00

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