Antibody-based vaccines for delivery of antigen to dendritic cells in situ
Antibody-based vaccines for delivery of antigen to dendritic cells in situ
Numerous studies have documented the crucial role of dendritic cells (DC) in the cross-priming of cytotoxic T-lymphocyte responses against exogenous antigens. However, these responses, particularly to tumour specific antigens, are often sub-optimal. Aiming to investigate the effectiveness of vaccines targeting antigen to DC in situ and their ability to potentiate immunity, we generated a panel of conjugates consisting of ovalbumin (Ova) protein linked to monoclonal antibodies (mAb) that target molecules expressed mainly on DC. The effectiveness of the various [FabxOva] conjugates was investigated in in vitro co-culture assays and in an in vivo system where Ova-specific CD8 and CD4 T cells were adoptively transferred into naïve mice. The results revealed that targeting of the integrin CD11c, induced the strongest CD4 and CD8 T cell responses, followed by DEC205 and MHC-II targeting. Co-administration with the adjuvant α-CD40 mAb, prevented the induction of tolerance and generated functional memory effector T cells. In addition, immunization with a single low dose of [α-CD11cxOva] had the unique ability to rapidly generate high titres of α-Ova IgG. Together with data from biodistribution studies, we demonstrate here that delivery of antigen to DC in situ, in particular via CD11c, can efficiently potentiate T and B cell immunity and propose that this molecule plays an important and as yet poorly characterized role in the transfer of intact antigen to B cells and possibly CD8+DC. Immunization with [α-CD11cxOva] was observed to enhance the resistance to tumour development and these encouraging results highlight the potential clinical benefit of this strategy in the treatment of cancer.
University of Southampton
Castro, Fernanda V. V. de
b5e0666f-f9e4-4ed6-9f6a-d2ed7ffd4f3b
2007
Castro, Fernanda V. V. de
b5e0666f-f9e4-4ed6-9f6a-d2ed7ffd4f3b
Castro, Fernanda V. V. de
(2007)
Antibody-based vaccines for delivery of antigen to dendritic cells in situ.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Numerous studies have documented the crucial role of dendritic cells (DC) in the cross-priming of cytotoxic T-lymphocyte responses against exogenous antigens. However, these responses, particularly to tumour specific antigens, are often sub-optimal. Aiming to investigate the effectiveness of vaccines targeting antigen to DC in situ and their ability to potentiate immunity, we generated a panel of conjugates consisting of ovalbumin (Ova) protein linked to monoclonal antibodies (mAb) that target molecules expressed mainly on DC. The effectiveness of the various [FabxOva] conjugates was investigated in in vitro co-culture assays and in an in vivo system where Ova-specific CD8 and CD4 T cells were adoptively transferred into naïve mice. The results revealed that targeting of the integrin CD11c, induced the strongest CD4 and CD8 T cell responses, followed by DEC205 and MHC-II targeting. Co-administration with the adjuvant α-CD40 mAb, prevented the induction of tolerance and generated functional memory effector T cells. In addition, immunization with a single low dose of [α-CD11cxOva] had the unique ability to rapidly generate high titres of α-Ova IgG. Together with data from biodistribution studies, we demonstrate here that delivery of antigen to DC in situ, in particular via CD11c, can efficiently potentiate T and B cell immunity and propose that this molecule plays an important and as yet poorly characterized role in the transfer of intact antigen to B cells and possibly CD8+DC. Immunization with [α-CD11cxOva] was observed to enhance the resistance to tumour development and these encouraging results highlight the potential clinical benefit of this strategy in the treatment of cancer.
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Published date: 2007
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Local EPrints ID: 466351
URI: http://eprints.soton.ac.uk/id/eprint/466351
PURE UUID: 1dffa339-8f46-4603-8f0f-bd620a0f3188
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Date deposited: 05 Jul 2022 05:12
Last modified: 16 Mar 2024 20:39
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Author:
Fernanda V. V. de Castro
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