Allergen-Associated Immunomodulators: Modifying Allergy Outcome.

The prevalence of allergies is increasing since mid twentieth century; however the underlying causes of this increase are not fully clear. Understanding the mechanism by which a harmless protein becomes an allergen provides us with the basis to prevent and treat these diseases. Although most studies on allergen immunogenicity have traditionally focused on structural properties of the proteins, it is increasingly clear that allergenicity cannot be determined only based on structural features of the allergenic proteins. In fact, allergens do not encounter human facings as isolated molecules but contained in complex mixtures of proteins, carbohydrates and lipids, such as pollen grains or foods. As a result, attention has lately been directed to examine whether allergen-associated molecules exhibit immune-regulatory properties. The present review aims to illustrate some examples of how non-protein molecules accompanying the allergen can modulate allergic responses.

Total serum immunoglobulin M levels are affected by immunomodulators in seabream (Sparus aurata L.).

Immunoglobulin M (IgM) is a major component of the teleost humoral immune system. Despite the significance of IgM levels as an immune parameter, there are relatively few studies on changes induced in its total levels in serum. This study examines the effects of several immunomodulators (vitamin A, chitin, yeast cells or levamisole, which act as immunostimulants, and crowding, hypoxia or anaesthetics, which act as stressors) upon the total serum IgM levels of non-immunized gilthead seabream (Sparus aurata L.). Total serum IgM levels of fish fed with the assayed immunostimulant-supplemented diets were statistically higher than those in fish fed a non-supplemented diet, especially in the case of levamisole. On the other hand, serum IgM levels of fish subjected to different stressors were not affected by crowding, hypoxia or certain anaesthetics. However, benzocaine and a narcotic dose of 2-phenoxyethanol provoked a great reduction, while quinaldine sulphate increased IgM levels to a significant degree. These results show how the seric IgM levels can be differently affected by some immunomodulators and the important role they may play in the regulation of total circulating IgM levels in seabream. The possibility of using total serum IgM for assessing immunostimulation, disease diagnosis and stress symptoms during fish farming is discussed.

Th1 adjuvant N-acetyl-D-glucosamine polymer up-regulates Th1 immunity but down-regulates Th2 immunity against a mycobacterial protein (MPB-59) in interleukin-10-knockout and wild-type mice.

Treatment of mice with heat-killed (HK) Mycobacterium bovis BCG or 1- to 10-microm chitin particles (nonantigenic N-acetyl-D-glucosamine polymers) is known to induce innate immune responses, including gamma interferon (IFN-gamma) production, which plays a Th1 adjuvant role. However, HK BCG further induces prostaglandin E2-releasing spleen macrophages (Mphi) (PGE2-Mphi), which potentially inhibit Th1 adjuvant activities. We found that chitin particles did not induce PGE2-Mphi formation. To further assess whether chitin has Th1 adjuvant effects, interleukin-10 (IL-10)-knockout (KO) mice and their wild-type (WT, C57BL/6) controls were immunized with a 30-kDa MPB-59 mycobacterial protein mixed with chitin. Immunization with MPB-59 alone induced Th2 responses, characterized by increases in total serum immunoglobulin E (IgE) and specific serum IgG1 levels and spleen Th2 cells producing IL-4, IL-5, and IL-10. No IFN-gamma-producing spleen Th1 cells, specific serum IgG2a, or delayed-type hypersensitivity (DTH) footpad reactions were detected. On the other hand, chitin-MPB-59 immunization significantly increased spleen Th1 responses, DTH reaction, and serum IgG2a levels along with decreases of Th2 responses. The magnitude of these Th1 adjuvant effects was greater in IL-10-KO mice than in WT mice. In contrast, immunization with HK BCG-MPB-59 showed little or no Th1 adjuvant effect. These data indicate that chitin has a unique Th1 adjuvant effect on the development of Th1 immunity against a mycobacterial antigen. IL-10 down-regulates the adjuvant effect of chitin.

Immune stimulating activity of two new chitosan containing adjuvant formulations.

Recombinant proteins have potential as both human and veterinary vaccine antigens, but they are often weakly immunogenic and immunization with recombinant proteins may not elicit a significant immune response that recognizes the native protein. This report describes the immune stimulating activity of two new adjuvant formulations, a zinc-chitosan particle formulation designed to bind to histidine tagged recombinant proteins; and an emulsion formulation containing chitosan. BALB/c mice vaccinated with formulations comprising recombinant beta-human chorionic gonadotropin (betahCG) and each adjuvant had prolonged high titer antibodies that recognized both the recombinant betahCG and native hCG. betahCG is an established target for immunocontraceptive vaccines and a potential target for tumor immunotherapy. Isotype analysis of these antibodies revealed an IgG1 response in mice immunized with zinc-chitosan particles and a mixed IgG1, IgG2a and IgG2b response with the emulsion. These chitosan based adjuvant formulations were effective in sensitizing mice and guinea pigs for antigen specific DTH responses, indicating that these adjuvants stimulate both B and T lymphocytes. The ability of these adjuvants to stimulate significant responses with a poorly immunogenic recombinant protein suggests that they may have potential in developing vaccines based on synthetic peptides and subunit antigens.