Loss of Sialic Acid Binding Domain Redirects Protein σ1 to Enhance M Cell-Directed Vaccination

Złotkowska, Dagmara; Maddaloni, Massimo; Riccardi, Carol; Walters, Nancy; Holderness, Kathryn; Callis, Gayle; Rynda‐Apple, Agnieszka; Pascual, David W.

doi:10.1371/journal.pone.0036182

Cited by 4 publications

(2 citation statements)

References 43 publications

(112 reference statements)

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“…Native pσ1 is comprised of a long fibrous tail that inserts into the virion and a globular head that protrudes from the virion and binds host cells. Regulatory elements within the tail include a sialic acid-binding domain (SIAB) and a trimerization domain (Zlotkowska et al 2012). Thus, it Copyright © 2022 Japanese Society for Plant Biotechnology is important that autoantigen sequences tethered to pσ1 do not interfere with the trimerization, SIAB, or head domains, as these are essential for trimerization and cell binding.…”

Section: Construction Of the Mbp-pσ1 Expression Cassette And In Silic...mentioning

confidence: 99%

Recombinant MBP-pσ1 expressed in soybean seeds delays onset and reduces developing disease in an animal model of multiple sclerosis

Robles

Reichenberg

Grissom

et al. 2022

Plant Biotechnology

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It is estimated that multiple sclerosis (MS) affects over 2.8 million people worldwide, with a prevalence that is expected to continue growing over time. Unfortunately, there is no cure for this autoimmune disease. For several decades, antigen-specific treatments have been used in animal models of experimental autoimmune encephalomyelitis (EAE) to demonstrate their potential for suppressing autoimmune responses. Successes with preventing and limiting ongoing MS disease have been documented using a wide variety of myelin proteins, peptides, autoantigen-conjugates, and mimics when administered by various routes. While those successes were not translatable in the clinic, we have learned a great deal about the roadblocks and hurdles that must be addressed if such therapies are to be useful. Reovirus sigma1 protein (pσ1) is an attachment protein that allows the virus to target M cells with high affinity. Previous studies showed that autoantigens tethered to pσ1 delivered potent tolerogenic signals and diminished autoimmunity following therapeutic intervention. In this proof-of-concept study, we expressed a model multi-epitope autoantigen (human myelin basic protein, MBP) fused to pσ1 in soybean seeds. The expression of chimeric MBP-pσ1 was stable over multiple generations and formed the necessary multimeric structures required for binding to target cells. When administered to SJL mice prophylactically as an oral therapeutic, soymilk formulations containing MBP-pσ1 delayed the onset of clinical EAE and significantly reduced developing disease. These results demonstrate the practicality of soybean as a host for producing and formulating immunemodulating therapies to treat autoimmune diseases.

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Section: Construction Of the Mbp-pσ1 Expression Cassette And In Silic...mentioning

confidence: 99%

Recombinant MBP-pσ1 expressed in soybean seeds delays onset and reduces developing disease in an animal model of multiple sclerosis

Robles

Reichenberg

Grissom

et al. 2022

Plant Biotechnology

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“…M cells are specialized ECs covering the Peyer’s, caecal and colonic patches. These cells deliver intact proteins and particles directly to the gut associated lymphoid tissues (GALT), and therefore may play an important role in the regulation of immunological reactions to dietary antigens [ 37 , 38 ].…”

Section: Main Textmentioning

confidence: 99%

Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

Bilsen¹,

Szłapka

Ojalvo

et al. 2017

Clin Transl Allergy

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BackgroundThe introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP).Main bodyThe proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell–cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential.ConclusionThe application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs.

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M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine

Yan

Fan

et al. 2014

Vaccine

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Loss of Sialic Acid Binding Domain Redirects Protein σ1 to Enhance M Cell-Directed Vaccination

Cited by 4 publications

References 43 publications

Recombinant MBP-pσ1 expressed in soybean seeds delays onset and reduces developing disease in an animal model of multiple sclerosis

Recombinant MBP-pσ1 expressed in soybean seeds delays onset and reduces developing disease in an animal model of multiple sclerosis

Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine

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