Mechanisms of Oral Tolerance to Soluble Protein Antigens

Pabst, Oliver; Cunha, André Pires da; Weiner, Howard L.

doi:10.1016/b978-0-12-415847-4.00041-0

Cited by 2 publications

(2 citation statements)

References 196 publications

(202 reference statements)

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“…Such diminished systemic responsiveness of T cells can interfere with the generation of protective T cell-dependent immunity. Mucosal tolerance has been amply demonstrated in numerous animal models ( 25 ) and also in humans ( 26 ), and it is more readily induced by soluble than by particulate antigens. Importantly, individuals with pre-existing, systemically acquired immune responses are refractory to the induction of mucosal tolerance ( 27 ).…”

Section: Separate and Independent: Mucosal And Systemic Immunitymentioning

confidence: 99%

Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission

Russell

Městecký

2022

Front. Immunol.

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SARS-CoV-2 is primarily an airborne infection of the upper respiratory tract, which on reaching the lungs causes the severe acute respiratory disease, COVID-19. Its first contact with the immune system, likely through the nasal passages and Waldeyer’s ring of tonsils and adenoids, induces mucosal immune responses revealed by the production of secretory IgA (SIgA) antibodies in saliva, nasal fluid, tears, and other secretions within 4 days of infection. Evidence is accumulating that these responses might limit the virus to the upper respiratory tract resulting in asymptomatic infection or only mild disease. The injectable systemic vaccines that have been successfully developed to prevent serious disease and its consequences do not induce antibodies in mucosal secretions of naïve subjects, but they may recall SIgA antibody responses in secretions of previously infected subjects, thereby helping to explain enhanced resistance to repeated (breakthrough) infection. While many intranasally administered COVID vaccines have been found to induce potentially protective immune responses in experimental animals such as mice, few have demonstrated similar success in humans. Intranasal vaccines should have advantage over injectable vaccines in inducing SIgA antibodies in upper respiratory and oral secretions that would not only prevent initial acquisition of the virus, but also suppress community spread via aerosols and droplets generated from these secretions.

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Section: Separate and Independent: Mucosal And Systemic Immunitymentioning

confidence: 99%

Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission

Russell

Městecký

2022

Front. Immunol.

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“…While the exact aetiology remains unknown, IBD is typically attributed to a breakdown in immune tolerance to commensal intestinal microbiota 4. The intestinal tract is an immunologically rich organ, containing the largest number and diversity of immune cells in the entire body 11 12. A vast number of predominantly CD4 + T cells and plasma cells reside in gastrointestinal-associated lymphoid tissues (GALTs) within the lamina propria 13.…”

Section: Introductionmentioning

confidence: 99%

Protocol for a double-blind, randomised, placebo-controlled pilot study for assessing the feasibility and efficacy of faecal microbiota transplant in a paediatric Crohn’s disease population: PediCRaFT Trial

et al. 2019

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IntroductionCrohn’s disease (CD) is a chronic inflammatory condition with transmural involvement of the gastrointestinal tract. Extraintestinal manifestations are common, and the disease burden on patients and the healthcare system is significant. While treatment options have expanded in recent years, they have mainly focused on dampening the immune response, thus carrying notable risks associated with long-term immunosuppression. Faecal microbiota transplant (FMT) targets inflammatory bowel disease (IBD) by modifying intestinal dysbiosis. Limited adult and paediatric data have demonstrated a favourable response to FMT in IBD; however, no randomised controlled trial has yet been published in paediatrics. This double-blind, randomised, placebo-controlled pilot study will assess feasibility and efficacy outcomes of FMT in a paediatric CD population.Methods and analysisForty-five patients between the ages of 3 and 17 years, with established CD or IBD unclassified, will be enrolled 2:1 to undergo FMT intervention or placebo control. Participants will undergo a colonoscopic infusion to the terminal ileum at baseline, followed by oral capsules two times per week for 6 weeks. Outcomes will be measured throughout the intervention period and 18 weeks of subsequent follow-up. Primary outcomes will assess feasibility, including patient recruitment, sample collection and rates of adverse events. Secondary outcomes will address clinical efficacy, including change in clinical response, change in urine metabolome and change in microbiome.Ethics and disseminationEthics approval from the local hospital research ethics board was obtained at the primary site (McMaster Children’s Hospital, Hamilton), with ethics pending at the secondary site (Centre Hospitalier Universitaire-Sainte-Justine, Montréal). RBX7455 and RBX2660 are human donor-sourced, microbiota-based therapeutic formulations. Both RBX7455 and RBX2660 are currently undergoing clinical trials to support potential US Food and Drug Administration approval. Approval to conduct this paediatric clinical trial was obtained from Health Canada’s Biologics and Genetic Therapies Directorate. The results of this trial will be published in peer-reviewed journals and will help inform a large, multicentre trial in the future.Trial registration numberNCT03378167; pre-results.

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Mechanisms of Oral Tolerance to Soluble Protein Antigens

Cited by 2 publications

References 196 publications

Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission

Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission

Protocol for a double-blind, randomised, placebo-controlled pilot study for assessing the feasibility and efficacy of faecal microbiota transplant in a paediatric Crohn’s disease population: PediCRaFT Trial

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