Competition between CTL narrows the immune response induced by prime-boost vaccination protocols.

Recombinant vaccines encoding strings of virus- or tumor-derived peptides and/or proteins are currently being designed for use against both cancer and infectious diseases. These vaccines aim to induce cytotoxic immune responses against several Ags simultaneously. We developed a novel tetramer-based...

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Main Authors: Palmowski, M, Choi, E, Hermans, I, Gilbert, S, Chen, J, Gileadi, U, Salio, M, Van Pel, A, Man, S, Bonin, E, Liljestrom, P, Dunbar, P, Cerundolo, V
Format: Journal article
Language:English
Published: 2002
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author Palmowski, M
Choi, E
Hermans, I
Gilbert, S
Chen, J
Gileadi, U
Salio, M
Van Pel, A
Man, S
Bonin, E
Liljestrom, P
Dunbar, P
Cerundolo, V
author_facet Palmowski, M
Choi, E
Hermans, I
Gilbert, S
Chen, J
Gileadi, U
Salio, M
Van Pel, A
Man, S
Bonin, E
Liljestrom, P
Dunbar, P
Cerundolo, V
author_sort Palmowski, M
collection OXFORD
description Recombinant vaccines encoding strings of virus- or tumor-derived peptides and/or proteins are currently being designed for use against both cancer and infectious diseases. These vaccines aim to induce cytotoxic immune responses against several Ags simultaneously. We developed a novel tetramer-based technique, based on chimeric HLA A2/H-2K(b) H chains, to directly monitor the CTL response to such vaccines in HLA-A2 transgenic mice. We found that priming and boosting with the same polyepitope construct induced immune responses that were dominated by CTL of a single specificity. When a mixture of viruses encoding single proteins was used to boost the polyepitope primed response, CTL of multiple specificities were simultaneously expanded to highly effective levels in vivo. In addition, we show that a preexisting response to one of the epitopes encoded within a polyepitope construct significantly impaired the ability of the vaccine to expand CTL of other specificities. Our findings define a novel vaccination strategy optimized for the induction of an effective polyvalent cytotoxic response.
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spelling oxford-uuid:c5763a8c-bb8d-4455-8a75-d30a6ae8cedb2022-03-27T06:31:07ZCompetition between CTL narrows the immune response induced by prime-boost vaccination protocols.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c5763a8c-bb8d-4455-8a75-d30a6ae8cedbEnglishSymplectic Elements at Oxford2002Palmowski, MChoi, EHermans, IGilbert, SChen, JGileadi, USalio, MVan Pel, AMan, SBonin, ELiljestrom, PDunbar, PCerundolo, VRecombinant vaccines encoding strings of virus- or tumor-derived peptides and/or proteins are currently being designed for use against both cancer and infectious diseases. These vaccines aim to induce cytotoxic immune responses against several Ags simultaneously. We developed a novel tetramer-based technique, based on chimeric HLA A2/H-2K(b) H chains, to directly monitor the CTL response to such vaccines in HLA-A2 transgenic mice. We found that priming and boosting with the same polyepitope construct induced immune responses that were dominated by CTL of a single specificity. When a mixture of viruses encoding single proteins was used to boost the polyepitope primed response, CTL of multiple specificities were simultaneously expanded to highly effective levels in vivo. In addition, we show that a preexisting response to one of the epitopes encoded within a polyepitope construct significantly impaired the ability of the vaccine to expand CTL of other specificities. Our findings define a novel vaccination strategy optimized for the induction of an effective polyvalent cytotoxic response.
spellingShingle Palmowski, M
Choi, E
Hermans, I
Gilbert, S
Chen, J
Gileadi, U
Salio, M
Van Pel, A
Man, S
Bonin, E
Liljestrom, P
Dunbar, P
Cerundolo, V
Competition between CTL narrows the immune response induced by prime-boost vaccination protocols.
title Competition between CTL narrows the immune response induced by prime-boost vaccination protocols.
title_full Competition between CTL narrows the immune response induced by prime-boost vaccination protocols.
title_fullStr Competition between CTL narrows the immune response induced by prime-boost vaccination protocols.
title_full_unstemmed Competition between CTL narrows the immune response induced by prime-boost vaccination protocols.
title_short Competition between CTL narrows the immune response induced by prime-boost vaccination protocols.
title_sort competition between ctl narrows the immune response induced by prime boost vaccination protocols
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