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Title: Antibody-based vaccines for delivery of antigen to dendritic cells in situ
Author: de Castro, Fernanda V. V.
ISNI:       0000 0001 3420 136X
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2007
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Numerous studies have documented the crucial role of dendritic cells (DC) in the cross-priming of cytotoxic T-Iymphocyte responses against exogenous antigens. However, these responses, particularly to tumour specific antigens, are often suboptimal. Aiming to investigate the effectiveness of vaccines targeting anti~en 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 CDS and CD4 T· cells were adoptively transferred into naive mice. The results revealed that targeting of the integrin CDllc, induced the strongest CD4 and CDS T cell responses, followed by DEC205 and MHC-II targeting. Co-administration with the adjuvant a-CD40 mAb, 'prevented the induction of tolerance and generated functional memory effector T cells. In addition, immunization with . a single lo. w dose of [a-CD11cxOva] had the unique ability to rapidly generate high titres of a-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 rpolecule plays an important and as yet poprly characterized role in the transfer of intact antigen to B cells and possibly CDS+DC. Immunization with [a-CDllcxOva] 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available