Carbohydrate-based adjuvants

García-Vello, Pilar; Speciale, Immacolata; Chiodo, Fabrizio; Molinaro, Antonio; Castro, Cristina De

doi:10.1016/j.ddtec.2020.09.005

Cited by 30 publications

(21 citation statements)

References 56 publications

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“…A number of studies have described the immunomodulatory properties of yeast polysaccharides and several polysaccharides have been pursued in clinics as adjuvants 7,8,41 . As a surrogate of yeast, zymosan is widely used for studying immunological properties of fungal polysaccharides.…”

Section: Discussionmentioning

confidence: 99%

Structural specificities of cell surface β-glucan polysaccharides determine commensal yeast mediated immuno-modulatory activities

et al. 2021

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Yeast is an integral part of mammalian microbiome, and like commensal bacteria, has the potential of being harnessed to influence immunity in clinical settings. However, functional specificities of yeast-derived immunoregulatory molecules remain elusive. Here we find that while under steady state, β-1,3-glucan-containing polysaccharides potentiate pro-inflammatory properties, a relatively less abundant class of cell surface polysaccharides, dubbed mannan/β-1,6-glucan-containing polysaccharides (MGCP), is capable of exerting potent anti-inflammatory effects to the immune system. MGCP, in contrast to previously identified microbial cell surface polysaccharides, through a Dectin1-Cox2 signaling axis in dendritic cells, facilitates regulatory T (Treg) cell induction from naïve T cells. Furthermore, through a TLR2-dependent mechanism, it restrains Th1 differentiation of effector T cells by suppressing IFN-γ expression. As a result, administration of MGCP display robust suppressive capacity towards experimental inflammatory disease models of colitis and experimental autoimmune encephalomyelitis (EAE) in mice, thereby highlighting its potential therapeutic utility against clinically relevant autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Structural specificities of cell surface β-glucan polysaccharides determine commensal yeast mediated immuno-modulatory activities

et al. 2021

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“…Carbohydrates and carbohydrate-containing molecules exert potent immunomodulatory effects on the innate immune system and have therefore shown adjuvant activity in pre-clinical and clinical studies ( Pedersen et al., 2018 ; Brown et al., 2018 ; Lang and Huang, 2020 ; Garcia-Vello et al., 2020 ; Pifferi et al., 2021 ). Carbohydrates interact with the innate immune system in a variety of ways, and often their mechanism of action is not completely understood.…”

Section: Carbohydrates As Vaccine Adjuvantsmentioning

confidence: 99%

Immunobiology of Carbohydrates: Implications for Novel Vaccine and Adjuvant Design Against Infectious Diseases

Stefanetti

Borriello

Richichi

et al. 2022

Front. Cell. Infect. Microbiol.

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Carbohydrates are ubiquitous molecules expressed on the surface of nearly all living cells, and their interaction with carbohydrate-binding proteins is critical to many immunobiological processes. Carbohydrates are utilized as antigens in many licensed vaccines against bacterial pathogens. More recently, they have also been considered as adjuvants. Interestingly, unlike other types of vaccines, adjuvants have improved immune response to carbohydrate-based vaccine in humans only in a few cases. Furthermore, despite the discovery of many new adjuvants in the last years, aluminum salts, when needed, remain the only authorized adjuvant for carbohydrate-based vaccines. In this review, we highlight historical and recent advances on the use of glycans either as vaccine antigens or adjuvants, and we review the use of currently available adjuvants to improve the efficacy of carbohydrate-based vaccines. A better understanding of the mechanism of carbohydrate interaction with innate and adaptive immune cells will benefit the design of a new generation of glycan-based vaccines and of immunomodulators to fight both longstanding and emerging diseases.

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“…These approaches have yielded promising pre-clinical results, including the induction of a balanced immune response and antigen dose sparing [ 94 , 95 , 96 , 97 ]. There are several ongoing and completed clinical trials investigating the safety and efficacy of carbohydrate adjuvants for infectious disease and cancer, such as chitosan (NCT00806962), β-glucan (NCT04936529), mannan [ 98 ], and crystalline δ-inulin under the trademark Advax TM (NCT05005559) [ 94 ], which have thus far suggested carbohydrate adjuvants can be well-tolerated and effective in humans at the doses necessary to confer an immunological benefit [ 98 , 99 , 100 ]. Carbohydrate PAMPs are also recognized by PRRs other than CLRs [ 54 , 94 , 100 ].…”

Section: Adjuvants With New Targetsmentioning

confidence: 99%

“…There are several ongoing and completed clinical trials investigating the safety and efficacy of carbohydrate adjuvants for infectious disease and cancer, such as chitosan (NCT00806962), β-glucan (NCT04936529), mannan [ 98 ], and crystalline δ-inulin under the trademark Advax TM (NCT05005559) [ 94 ], which have thus far suggested carbohydrate adjuvants can be well-tolerated and effective in humans at the doses necessary to confer an immunological benefit [ 98 , 99 , 100 ]. Carbohydrate PAMPs are also recognized by PRRs other than CLRs [ 54 , 94 , 100 ]. For instance, the previously mentioned saponin QS-21 adjuvant is already licensed for use as part of AS01, but is not known to interact with any CLRs [ 94 ].…”

Section: Adjuvants With New Targetsmentioning

confidence: 99%

Novel Vaccine Adjuvants as Key Tools for Improving Pandemic Preparedness

Pogostin

McHugh

2021

Bioengineering

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Future infectious disease outbreaks are inevitable; therefore, it is critical that we maximize our readiness for these events by preparing effective public health policies and healthcare innovations. Although we do not know the nature of future pathogens, antigen-agnostic platforms have the potential to be broadly useful in the rapid response to an emerging infection—particularly in the case of vaccines. During the current COVID-19 pandemic, recent advances in mRNA engineering have proven paramount in the rapid design and production of effective vaccines. Comparatively, however, the development of new adjuvants capable of enhancing vaccine efficacy has been lagging. Despite massive improvements in our understanding of immunology, fewer than ten adjuvants have been approved for human use in the century since the discovery of the first adjuvant. Modern adjuvants can improve vaccines against future pathogens by reducing cost, improving antigen immunogenicity, and increasing antigen stability. In this perspective, we survey the current state of adjuvant use, highlight potentially impactful preclinical adjuvants, and propose new measures to accelerate adjuvant safety testing and technology sharing to enable the use of “off-the-shelf” adjuvant platforms for rapid vaccine testing and deployment in the face of future pandemics.

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Carbohydrate-based adjuvants

Cited by 30 publications

References 56 publications

Structural specificities of cell surface β-glucan polysaccharides determine commensal yeast mediated immuno-modulatory activities

Structural specificities of cell surface β-glucan polysaccharides determine commensal yeast mediated immuno-modulatory activities

Immunobiology of Carbohydrates: Implications for Novel Vaccine and Adjuvant Design Against Infectious Diseases

Novel Vaccine Adjuvants as Key Tools for Improving Pandemic Preparedness

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