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The combined CTA1-DD/ISCOM adjuvant vector promotes priming of mucosal and systemic immunity to incorporated antigens by specific targeting of B cells.

Review article
Authors Anja Helgeby
Neil C Robson
Anne M Donachie
Helen Beackock-Sharp
Karin Lövgren
Karin Schön
Allan Mowat
Nils Y Lycke
Published in Journal of immunology (Baltimore, Md. : 1950)
Volume 176
Issue 6
Pages 3697-706
ISSN 0022-1767
Publication year 2006
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 3697-706
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adjuvants, Immunologic, Animals, Antibodies, immunology, metabolism, Antigens, immunology, B-Lymphocytes, immunology, Cholera Toxin, immunology, metabolism, ISCOMs, immunology, metabolism, Immunity, Mucosal, immunology, Lymph Nodes, metabolism, Mice, Recombinant Fusion Proteins, immunology, metabolism, Th1 Cells, immunology, Th2 Cells, immunology
Subject categories Medical and Health Sciences

Abstract

The cholera toxin A1 (CTA1)-DD/QuilA-containing, immune-stimulating complex (ISCOM) vector is a rationally designed mucosal adjuvant that greatly potentiates humoral and cellular immune responses. It was developed to incorporate the distinctive properties of either adjuvant alone in a combination that exerted additive enhancing effects on mucosal immune responses. In this study we demonstrate that CTA1-DD and an unrelated Ag can be incorporated together into the ISCOM, resulting in greatly augmented immunogenicity of the Ag. To demonstrate its relevance for protection against infectious diseases, we tested the vector incorporating PR8 Ag from the influenza virus. After intranasal immunization we found that the immunogenicity of the PR8 proteins were significantly augmented by a mechanism that was enzyme dependent, because the presence of the enzymatically inactive CTA1R7K-DD mutant largely failed to enhance the response over that seen with ISCOMs alone. The combined vector was a highly effective enhancer of a broad range of immune responses, including specific serum Abs and balanced Th1 and Th2 CD4(+) T cell priming as well as a strong mucosal IgA response. Unlike unmodified ISCOMs, Ag incorporated into the combined vector could be presented by B cells in vitro and in vivo as well as by dendritic cells; it also accumulated in B cell follicles of draining lymph nodes when given s.c. and stimulated much enhanced germinal center reactions. Strikingly, the enhanced adjuvant activity of the combined vector was absent in B cell-deficient mice, supporting the idea that B cells are important for the adjuvant effects of the combined CTA1-DD/ISCOM vector.

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