Investigating the contributions of inflammation and antigen depot to adjuvant function

Brewer, James M., Rush, Catherine M., and Garside, Paul (2006) Investigating the contributions of inflammation and antigen depot to adjuvant function. In: Vella, Anthony T., (ed.) Towards and Understanding of Initiating T Cell Immunity. Research Signpost, Kerala, India, pp. 1-23.

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Although we may think that we understand how vaccine adjuvants work, we cannot satisfactorily explain why certain vaccine adjuvants and/or delivery systems are more or less effective at inducing immune responses, or indeed why they promote the induction of particular types of response. A number of in vitro studies indicate that T cell activation, differentiation and function are regulated by APC factors, specifically the phenotype and activation state of APCs as well as the magnitude and duration of their antigen presentation. While it appears that adjuvants mediate their effects indirectly via APCs, it is unclear how, or if, any of the APC parameters noted above are influenced by vaccine adjuvants. Generalising the relationships between adjuvants and APC function is confounded by the diversity of adjuvant formulations available, for example various combinations of depot forming and inflammatory adjuvants. Importantly, few if any, of the APC factors defined above have been defined for these agents in vivo. This is a significant omission, as it is clear that the component parts of the immune system do not work in isolation and their interactions are dynamic and occur in distinct and specialised micro- and macroanatomical locations that can only be fully determined in real time, in the physiological context, in vivo. Therefore, in this article, we will review studies analysing the impact that adjuvants have on the phenotype, activation state and processing and presenting capacity of APC and the subsequent consequences for T cell activation, differentiation and function. Such studies have generally been performed in vitro, however, only by performing such detailed and fundamental studies in vivo can we fully understand the cellular and molecular interactions that control the immune response. This information is a prerequisite if we are truly to design, build and target vaccines and therapeutic strategies effectively.

Item ID: 9337
Item Type: Book Chapter (Research - B1)
ISBN: 978-81-308-0118-6
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Date Deposited: 10 May 2010 06:46
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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