E. coli Nissle 1917 is a safe mucosal delivery vector for a birch-grass pollen chimera to prevent allergic poly-sensitization

Sarate, Priya; Heinl, Stefan; Poiret, Sabine; Drinić, Mirjana; Zwicker, C.; Schabussova, Irma; Daniel, Catherine; Wiedermann, Ursula

doi:10.1038/s41385-018-0084-6

Cited by 30 publications

(31 citation statements)

References 47 publications

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“…In human patients as well as in surrogate mouse models, allergic asthma leads to an influx of inflammatory cells and cytokines into the lungs and mucus hyperproduction [ 22 , 36 , 50 , 51 , 52 , 53 , 54 ]. Although the measurement of these parameters in BALF is simple, BALF sampling in humans requires local anesthesia, and complications, such as coughing, bleeding, and fever, have been reported [ 55 , 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Machine Learning-Empowered FTIR Spectroscopy Serum Analysis Stratifies Healthy, Allergic, and SIT-Treated Mice and Humans

et al. 2020

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The unabated global increase of allergic patients leads to an unmet need for rapid and inexpensive tools for the diagnosis of allergies and for monitoring the outcome of allergen-specific immunotherapy (SIT). In this proof-of-concept study, we investigated the potential of Fourier-Transform Infrared (FTIR) spectroscopy, a high-resolution and cost-efficient biophotonic method with high throughput capacities, to detect characteristic alterations in serum samples of healthy, allergic, and SIT-treated mice and humans. To this end, we used experimental models of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific tolerance induction in BALB/c mice. Serum collected before and at the end of the experiment was subjected to FTIR spectroscopy. As shown by our study, FTIR spectroscopy, combined with deep learning, can discriminate serum from healthy, allergic, and tolerized mice, which correlated with immunological data. Furthermore, to test the suitability of this biophotonic method for clinical diagnostics, serum samples from human patients were analyzed by FTIR spectroscopy. In line with the results from the mouse models, machine learning-assisted FTIR spectroscopy allowed to discriminate sera obtained from healthy, allergic, and SIT-treated humans, thereby demonstrating its potential for rapid diagnosis of allergy and clinical therapeutic monitoring of allergic patients.

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Section: Discussionmentioning

confidence: 99%

Machine Learning-Empowered FTIR Spectroscopy Serum Analysis Stratifies Healthy, Allergic, and SIT-Treated Mice and Humans

et al. 2020

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“…Two recombinant strains EcN previously described ( 28 ) were used in the current study: i) EcN-Chim: a clone expressing multi-allergen chimer Phl p 5-Bet v 1-Phl p 1 along with fluorescent mCherry; ii) EcN-Ctrl clone expressing only mCherry without allergen. Both recombinant clones were grown and selected on Luria-Bertani (LB) agar plates with 20 µg ml −1 chloramphenicol (CM) at 37°C overnight, as described in Sarate et al, 2019 ( 28 ). In liquid medium, recombinant EcN-Chim and EcN-Ctrl strains were cultivated at 30°C on 200 RPM overnight in LB-medium containing 20 µg/ml chloramphenicol ( 28 ).…”

Section: Methodsmentioning

confidence: 99%

“…Both recombinant clones were grown and selected on Luria-Bertani (LB) agar plates with 20 µg ml −1 chloramphenicol (CM) at 37°C overnight, as described in Sarate et al, 2019 ( 28 ). In liquid medium, recombinant EcN-Chim and EcN-Ctrl strains were cultivated at 30°C on 200 RPM overnight in LB-medium containing 20 µg/ml chloramphenicol ( 28 ).…”

Section: Methodsmentioning

confidence: 99%

“…Here, we investigated whether Escherichia coli Nissle 1917 (EcN), a probiotic Gram-negative bacterial strain with strong immunomodulatory properties ( 27 , 28 ), can prevent the development of poly-sensitization in mice when applied early in life. Recently, we engineered a recombinant EcN expressing either the major birch (Bet v 1) and grass (Phl p 1 and Phl p 5) (EcN-Chim) pollen allergens or EcN harboring the empty plasmid (EcN-Ctrl) ( 7 , 28 , 29 ) and showed that the intranasal pretreatment with EcN-Chim but not EcN-Ctrl reduced allergic poly-sensitization in adult mice ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

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Pre- and Neonatal Imprinting on Immunological Homeostasis and Epithelial Barrier Integrity by Escherichia coli Nissle 1917 Prevents Allergic Poly-Sensitization in Mice

et al. 2021

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A steady rise in the number of poly-sensitized patients has increased the demand for effective prophylactic strategies against multi-sensitivities. Probiotic bacteria have been successfully used in clinics and experimental models to prevent allergic mono-sensitization. In the present study, we have investigated whether probiotic bacteria could prevent poly-sensitization by imprinting on the immune system early in life. We used two recombinant variants of probiotic Escherichia coli Nissle 1917 (EcN): i) EcN expressing birch and grass pollen, poly-allergen chimera construct (EcN-Chim), and ii) an “empty” EcN without allergen expression (EcN-Ctrl). Conventional mice (CV) were treated with either EcN-Chim or EcN-Ctrl in the last week of the gestation and lactation period. Gnotobiotic mice received one oral dose of either EcN-Chim or EcN-Ctrl before mating. The offspring from both models underwent systemic allergic poly-sensitization and intranasal challenge with recombinant birch and grass pollen allergens (rBet v 1, rPhl p 1, and rPhl p 5). In the CV setting, the colonization of offspring via treatment of mothers reduced allergic airway inflammation (AAI) in offspring compared to poly-sensitized controls. Similarly, in a gnotobiotic model, AAI was reduced in EcN-Chim and EcN-Ctrl mono-colonized offspring. However, allergy prevention was more pronounced in the EcN-Ctrl mono-colonized offspring as compared to EcN-Chim. Mono-colonization with EcN-Ctrl was associated with a shift toward mixed Th1/Treg immune responses, increased expression of TLR2 and TLR4 in the lung, and maintained levels of zonulin-1 in lung epithelial cells as compared to GF poly-sensitized and EcN-Chim mono-colonized mice. This study is the first one to establish the model of allergic poly-sensitization in gnotobiotic mice. Using two different settings, gnotobiotic and conventional mice, we demonstrated that an early life intervention with the EcN without expressing an allergen is a powerful strategy to prevent poly-sensitization later in life.

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“…Big advantages of recombinant hypoallergenic derivatives for a potential use in preventive AIT approaches are that they represent defined molecules with known properties, which can be produced under GMP conditions in a reproducible manner [21,22,121 ▪ ,122]. In fact, hypoallergenic allergen derivatives have already been used for immunization in nonallergic individuals in two small clinical trials [123,124 ▪▪ ].…”

Section: Allergen-specific Forms Of Prevention Are On the Horizonmentioning

confidence: 99%

Recombinant allergens for immunotherapy: state of the art

Zhernov

Curin

Khaitov

et al. 2019

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review More than 30 years ago, the first molecular structures of allergens were elucidated and defined recombinant allergens became available. We review the state of the art regarding molecular AIT with the goal to understand why progress in this field has been slow, although there is huge potential for treatment and allergen-specific prevention. Recent findings On the basis of allergen structures, several AIT strategies have been developed and were advanced into clinical evaluation. In clinical AIT trials, promising results were obtained with recombinant and synthetic allergen derivatives inducing allergen-specific IgG antibodies, which interfered with allergen recognition by IgE whereas clinical efficacy could not yet be demonstrated for approaches targeting only allergen-specific T-cell responses. Available data suggest that molecular AIT strategies have many advantages over allergen extract-based AIT. Summary Clinical studies indicate that recombinant allergen-based AIT vaccines, which are superior to existing allergen extract-based AIT can be developed for respiratory, food and venom allergy. Allergen-specific preventive strategies based on recombinant allergen-based vaccine approaches and induction of T-cell tolerance are on the horizon and hold promise that allergy can be prevented. However, progress is limited by lack of resources needed for clinical studies, which are necessary for the development of these innovative strategies.

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E. coli Nissle 1917 is a safe mucosal delivery vector for a birch-grass pollen chimera to prevent allergic poly-sensitization

Cited by 30 publications

References 47 publications

Machine Learning-Empowered FTIR Spectroscopy Serum Analysis Stratifies Healthy, Allergic, and SIT-Treated Mice and Humans

Machine Learning-Empowered FTIR Spectroscopy Serum Analysis Stratifies Healthy, Allergic, and SIT-Treated Mice and Humans

Pre- and Neonatal Imprinting on Immunological Homeostasis and Epithelial Barrier Integrity by Escherichia coli Nissle 1917 Prevents Allergic Poly-Sensitization in Mice

Recombinant allergens for immunotherapy: state of the art

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