Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.

The orthodox role of the invariant chain (CD74; Ii) is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the ma...

Full description

Bibliographic Details
Main Authors: Spencer, A, Cottingham, M, Jenks, J, Longley, R, Capone, S, Colloca, S, Folgori, A, Cortese, R, Nicosia, A, Bregu, M, Hill, A
Format: Journal article
Language:English
Published: Public Library of Science 2014
_version_ 1797070361915817984
author Spencer, A
Cottingham, M
Jenks, J
Longley, R
Capone, S
Colloca, S
Folgori, A
Cortese, R
Nicosia, A
Bregu, M
Hill, A
author_facet Spencer, A
Cottingham, M
Jenks, J
Longley, R
Capone, S
Colloca, S
Folgori, A
Cortese, R
Nicosia, A
Bregu, M
Hill, A
author_sort Spencer, A
collection OXFORD
description The orthodox role of the invariant chain (CD74; Ii) is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA), higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required.
first_indexed 2024-03-06T22:37:42Z
format Journal article
id oxford-uuid:5a7bb313-8771-4074-8026-2a310727daa6
institution University of Oxford
language English
last_indexed 2024-03-06T22:37:42Z
publishDate 2014
publisher Public Library of Science
record_format dspace
spelling oxford-uuid:5a7bb313-8771-4074-8026-2a310727daa62022-03-26T17:16:01ZEnhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5a7bb313-8771-4074-8026-2a310727daa6EnglishSymplectic Elements at OxfordPublic Library of Science2014Spencer, ACottingham, MJenks, JLongley, RCapone, SColloca, SFolgori, ACortese, RNicosia, ABregu, MHill, AThe orthodox role of the invariant chain (CD74; Ii) is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA), higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required.
spellingShingle Spencer, A
Cottingham, M
Jenks, J
Longley, R
Capone, S
Colloca, S
Folgori, A
Cortese, R
Nicosia, A
Bregu, M
Hill, A
Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.
title Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.
title_full Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.
title_fullStr Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.
title_full_unstemmed Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.
title_short Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.
title_sort enhanced vaccine induced cd8 t cell responses to malaria antigen me trap by fusion to mhc class ii invariant chain
work_keys_str_mv AT spencera enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT cottinghamm enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT jenksj enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT longleyr enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT capones enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT collocas enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT folgoria enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT corteser enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT nicosiaa enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT bregum enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain
AT hilla enhancedvaccineinducedcd8tcellresponsestomalariaantigenmetrapbyfusiontomhcclassiiinvariantchain