Glucans as Immunological Adjuvants

Mohagheghpour, Nahid; Dawson, Marcia I.; Hobbs, Peter D.; Judd, Amrit K.; Winant, Richard C.; Dousman, Linda; Waldeck, N; Hokama, Leslie A.; Tusé, Daniel; Kos, Ferdynand; Benike, Claudia; Engleman, Edgar G.

doi:10.1007/978-1-4615-1891-4_3

Cited by 25 publications

(19 citation statements)

References 22 publications

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“…37) Although various immunopharmacological activities of b-glucans have been examined extensively, 1) there are only a limited number of studies on the adjuvant effects of b-glucans on antibody production. 33,37) The biological effects on antibody production of gel-forming b-glucans possessing various physicochemical properties are not fully understood. Therefore, we investigated the adjuvant effects of various gel-forming b-glucans, GRN, SSG and SPG, using mice immunized with the soluble antigen TNP-OVA.…”

Section: Discussionmentioning

confidence: 99%

“…25) Polarized Th1 and Th2 phenotypes play a central role in the course of autoimmune and infectious diseases. 25) Although there are some reports showing an adjuvant effect of b-glucans, [33][34][35] most of those studies were performed using particulate or triple helical b-glucans. In our previous studies, we proved that GRN has an adjuvant effect, 36) but we have not examined possible differential effects of these bglucans on Th1-and Th2-dependent antibody production.…”

Section: (1→6)-branched (1→3)-b-d-glucans (B-glucans) Frommentioning

confidence: 99%

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Th1/Th2-Balancing Immunomodulating Activity of Gel-Forming (1.RAR.3)-.BETA.-Glucans from Fungi.

Suzuki

Adachi

Ohno

et al. 2001

Biological & Pharmaceutical Bulletin

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(1→6)-branched (1→3)-b-D-glucans (b-glucans) fromfungi are known to enhance various immunopharmacological activities such as antitumor activity.1) Some of them, including lentinan 2) and sonifilan (SPG), 3) have been used clinically for cancer therapy in Japan. We have been investigating various immunopharmacological effects of b-glucans, such as grifolan (GRN) from Grifola frondasa 4) and sclerotinia sclerotiorum glucan (SSG) 5) from Sclerotinia sclerotiorum IFO 9395, which were isolated originally by our group. GRN has a similar primary structure to SPG,4) but SSG consists of a b-(1→3)-polyglucose backbone with every second residue substituted with mono-glucosyl branches. 5,6) The ultrastructure of GRN and SSG is distinct from that of SPG.7) GRN and SSG contain a mixture of single and triple helix conformers, whereas SPG is composed of triple helixes only. 8,9) The molecular weight of a single chain of SPG is 15 kDa, which is much lower than those of GRN (50 kDa) and SSG (200 kDa). 5,6,10) Our accumulated data suggest that the molecular weight, degree of branching, number of substituents, as well as ultrastructure, including the presence of single and triple helixes, significantly affects the biological activities of b-glucans. [11][12][13][14] For instance, it was demonstrated that GRN and SSG could more markedly induce various activities of immunological cells such as cytotoxic T cells and macrophages than SPG, although the antitumor effects of these two glucans were similar to those of SPG.15) Using SPG and SPG-OH, which is a single helical conformer prepared by alkaline treatment of SPG, we also found previously that the biological activities of b-glucans, i.e. blood clearance, 16) reactivity of limulus factor G activation, 17) and NO synthesis in vivo 18) and in vitro, are strongly associated with their conformation. 8,19) However we do not yet know the details of activities of various b-glucans on helper T cell modulation.T cell responses have been divided in two subclasses, Th1and Th2, according to the profile of the lymphokines produced, i.e., IFN-g and IL-2 vs. IL-4, IL-5, and IL-10, respectively. 20) Evidence is accumulating that cytokines play a role during T helper cell differentiation. IL-4 has a direct effect on the induction of IL-4-producing Th2 cells 21) and IFN-g causes the preferential outgrowth of Th1. 22) In addition, IL-4 appears to inhibit the induction of Th1 cells in vitro and in vivo. 23,24) Antigen-presenting cells such as macrophages and dendritic cells also play a major role in T helper cell differentiation. IL-12 derived from antigen-presenting cells stimulates IFN-g production from T cells and NK cells, thereby favoring a Th1-pattern of response. 25,26) There is clear evidence that IL-12 can suppress IL-4 mRNA induction, both directly and indirectly, through induction of 28) In the antibody response, IgG2a responses are induced by IFNg and suppressed by IL-4. 29) IFN-g promotes isotype switching to IgG2a.30,31) IL-12 also stimulates the production of IgG2a, presumably through i...

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Section: Discussionmentioning

confidence: 99%

Section: (1→6)-branched (1→3)-b-d-glucans (B-glucans) Frommentioning

confidence: 99%

Th1/Th2-Balancing Immunomodulating Activity of Gel-Forming (1.RAR.3)-.BETA.-Glucans from Fungi.

Suzuki

Adachi

Ohno

et al. 2001

Biological & Pharmaceutical Bulletin

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“…Several studies have demonstrated the adjuvant effect of glucans when co-administered with either bacterial, fungal, protozoa or viral antigens [13, 144,168]. In all these studies, ß-glucans were administered via the parental route.…”

Section: Dectin-1-bindingmentioning

confidence: 99%

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

et al. 2006

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-In developing veterinary mucosal vaccines and vaccination strategies, mucosal adjuvants are one of the key players for inducing protective immune responses. Most of the mucosal adjuvants seem to exert their effect via binding to a receptor/or target cells and these properties were used to classify the mucosal adjuvants reviewed in the present paper: (1) ganglioside receptor-binding toxins (cholera toxin, LT enterotoxin, their B subunits and mutants); (2) surface immunoglobulin binding complex CTA1-DD; (3) TLR4 binding lipopolysaccharide; (4) TLR2-binding muramyl dipeptide; (5) Mannose receptor-binding mannan; (6) Dectin-1-binding ß 1,3/1,6 glucans; (7) TLR9-binding CpG-oligodeoxynucleotides; (8) Cytokines and chemokines; (9) Antigen-presenting cell targeting ISCOMATRIX and ISCOM. In addition, attention is given to two adjuvants able to prime the mucosal immune system following a systemic immunization, namely 1α, 25(OH) 2 D 3 and cholera toxin.

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“…Алгал стимулирует гуморальный и клеточ-ный иммунный ответ на введение пептидных антигенов глико-протеина D вируса герпеса [39].…”

Section: бета-глюкановые адъювантыunclassified

“…Множество описанных выше адъювантов на основе по-лисахаридов, в том числе зимозан, маннан, MDP и ЛПС, действуют путем активации таких рецепторов врожденного иммунитета, как TLR, NOD2 и лектины С-типа, что вызывает продукцию провоспалительных цитокинов, которая приво-дит к усилению иммуногенности вакцины [39,75]. Ряд угле-водных адъювантов, в том числе MDP, ЛПС, зимозан, маннан, β-глюкан и дельта-инулин, активируют комплемент, что также может способствовать их адъювантной активности [76,77].…”

Section: механизмы адъювантного действия углеводовunclassified