Oral vaccination with immune stimulating complexes

Mowat, A. M., Smith, R. E., Donachie, A. M., Furrie, E., Grdic, D. and Lycke, N. (1999) Oral vaccination with immune stimulating complexes. Immunology Letters, 65(1-2), pp. 133-140. (doi:10.1016/S0165-2478(98)00136-9)

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Publisher's URL: http://dx.doi.org/10.1016/S0165-2478(98)00136-9

Abstract

There is a need for non-living adjuvant vectors which will induce a full range of local and systemic immune responses to orally administered purified antigens. Here we describe our experience with lipophilic immune stimulating complexes (ISCOMS) containing the saponin adjuvant Quil A. When given orally, ISCOMS containing the model protein antigen ovalbumin (OVA) induce a wide range of systemic immune responses, including Th1 and Th2 CD4 dependent activity, class I MHC restricted cytotoxic T-cell responses and local production of secretory IgA antibodies. More recent results indicate that ISCOMS may act partly by enhancing the uptake of protein from the gut. In addition, intraperitoneal injection of ISCOMS recruits and activates many components of the innate immune system, including neutrophils, macrophages, and dendritic cells. In parallel, there is increased production of nitric oxide (NO), reactive oxygen intermediates (ROI), interleukins (IL) 1, 6, 12, and γ interferon (γIFN). Of these factors, only IL12 is essential for the immunogenicity of ISCOMS in vivo, as mucosal and systemic responses to ISCOMS are reduced in IL12KO mice, but not in IL4KO, IL6KO, inducible NO synthase (iNOS) KO, or γIFN receptor KO mice. We propose that ISCOMS act by targetting antigen and adjuvant to macrophages and/or dendritic cells. This pathway may be amenable to exploitation for vaccine development, especially if combined with another vector with a different mucosal adjuvant profile, such as cholera toxin.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mowat, Professor Allan and Donachie, Ms Anne Marie
Authors: Mowat, A. M., Smith, R. E., Donachie, A. M., Furrie, E., Grdic, D., and Lycke, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology Letters
Publisher:Elsevier
ISSN:0165-2478
ISSN (Online):1879-0542

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