Fel d 1-airway inflammation prevention and treatment by co-immunization vaccine via induction of CD4+CD25-Foxp3+ Treg cells

Pei, Yechun; Geng, Shuang; Liu, Lin; Yan, Fengxiang; Hong, Guan; Hou, Jian; Chen, Yongfu; Wang, Bin; An, Xiao-Rong

doi:10.4161/hv.23518

Cited by 6 publications

(3 citation statements)

References 49 publications

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“…Even after repeated monthly exposure to aerosolized allergen, an initially set protective TH‐1 bias did not end up in pathological TH‐1‐mediated inflammation . Alongside with the above‐mentioned importance of modulating the allergen‐driven TH‐2 response toward TH‐1, we and others also observed induction of regulatory T cells following immunization with plasmid DNA . Likewise, protection did not necessarily correlate with total levels of IFN‐γ, suggesting that besides IFN‐γ production other mechanisms might play a role in protection from allergic responses after plasmid‐based immunization.…”

Section: Mimicking the Healthy Statusmentioning

confidence: 57%

DNA and mRNA vaccination against allergies

Scheiblhofer

Thalhamer

Weiss

2018

Pediatric Allergy Immunology

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Allergen‐specific immunotherapy, which is performed by subcutaneous injection or sublingual application of allergen extracts, represents an effective treatment against type I allergic diseases. However, due to the long duration and adverse reactions, only a minority of patients decides to undergo this treatment. Alternatively, early prophylactic intervention in young children has been proposed to stop the increase in patient numbers. Plasmid DNA and mRNA vaccines encoding allergens have been shown to induce T helper 1 as well as T regulatory responses, which modulate or counteract allergic T helper 2–biased reactions. With regard to prophylactic immunization, additional safety measurements are required. In contrast to crude extracts, genetic vaccines provide the allergen at high purity. Moreover, by targeting the encoded allergen to subcellular compartments for degradation, release of native allergen can be avoided. Due to inherent safety features, mRNA vaccines could be the candidates of choice for preventive allergy immunizations. The subtle priming of T helper 1 immunity induced by this vaccine type closely resembles responses of non‐allergic individuals and—by boosting via natural allergen exposure—could suffice for long‐term protection from type I allergy.

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Section: Mimicking the Healthy Statusmentioning

confidence: 57%

DNA and mRNA vaccination against allergies

Scheiblhofer

Thalhamer

Weiss

2018

Pediatric Allergy Immunology

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“…In contrast, a two-year grass pollen AIT did not lead to any increase in Treg cell responses and, thus, failed to offer long-term protection despite its effectiveness in reducing CRTH2 + CCR4 + CD27-CD4 + Th2 cells and in desensitizing patients [38]. Similar to other successful AIT [39], the CD4 + CD25 + Foxp3 + Treg cell population detected in the spleen was highly elevated in both pMEM49- and pMED171-treated mice when compared with the controls. Interestingly, the magnitude of systemic Foxp3 + Treg cell expansion was much higher in the pMED171-treated mice.…”

Section: Discussionmentioning

confidence: 99%

Modulating Shrimp Tropomyosin-Mediated Allergy: Hypoallergen DNA Vaccines Induce Regulatory T Cells to Reduce Hypersensitivity in Mouse Model

Wai

Leung

et al. 2019

IJMS

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Shellfish allergy is one of the most common food allergies, with tropomyosin as the major cross-reactive allergen. However, no allergen-specific immunotherapy is clinically available. Recently, we designed two shrimp hypoallergens MEM49 and MED171. This study aimed to examine and compare the efficacy of the MEM49- and MED171-based DNA vaccines (pMEM49 and pMED171) in modulating shrimp allergy in a murine model of shrimp tropomyosin sensitivity. Intradermal immunization of BALB/c mice with pMEM49 or pMED171 effectively down-modulated allergic symptoms, tropomyosin-specific IgE levels, intestinal Th2 cytokines expression, and inflammatory cell infiltration. Both pMEM49 and pMED171 increased the frequency of regulatory T cells, but to a greater extent by pMED171 with upregulation of gut-homing molecules integrin-α4β7. The functionality of the pMED171-induced Treg cells was further illustrated by anti-CD25-mediated depletion of Treg cells and the adoptive transfer of CD4+CD25+Foxp3+Treg cells. Collectively, the data demonstrate that intradermal administration of pMED171 leads to the priming, activation, and migration of dermal dendritic cells which subsequently induce Treg cells, both locally and systemically, to downregulate the allergic responses to tropomyosin. This study is the first to demonstrate the potency of hypoallergen-encoding DNA vaccines as a therapeutic strategy for human shellfish allergy via the vigorous induction of functional Treg cells.

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“…Both, regulatory 33 - 35 as well as Th1 23 - 25 T-cell responses have been shown to be induced by genetic vaccines, protecting from allergic sensitization in animal models. Therefore, prophylactic vaccination against allergy can be regarded as a true protective vaccination mimicking one of the strategies nature uses to mount healthy immune responses.…”

Section: Protective Immunity Against Allergymentioning

confidence: 99%

Allergens are not pathogens

Weiss

Scheiblhofer

Thalhamer

2013

Human Vaccines & Immunotherapeutics

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Vaccination against infectious diseases has been one of the major breakthroughs in human medical history, saving the lives of millions of people each year. More recently, prophylactic vaccination against non-infectious diseases such as cancer, Alzheimer’s disease, diabetes, and type I allergy is being investigated. Particularly in case of IgE-driven allergic disorders, which afflict almost a quarter of the population in highly developed countries, preventative measures would represent a major improvement for patients’ health as well as an economic relief for public health services. As an alternative to allergen-specific immunotherapy, prophylactic vaccination against type I allergic diseases could slow down or even stop the progress of the allergy pandemic. Allergen-encoding gene-based vaccines, i.e., plasmid DNA and mRNA vaccines, provide the advantage of purity over crude allergen extracts, which involve the risk of de novo sensitizations. Furthermore, these formulations have been demonstrated to induce T helper 1 as well as T regulatory immune responses—a pre-requisite for prophylactic intervention against allergies. However, prophylactic vaccines against environmental allergens strikingly differ from conventional vaccines against infectious diseases or therapeutic approaches concerning the underlying immunological mechanisms.

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Fel d 1-airway inflammation prevention and treatment by co-immunization vaccine via induction of CD4+CD25-Foxp3+ Treg cells

Cited by 6 publications

References 49 publications

DNA and mRNA vaccination against allergies

DNA and mRNA vaccination against allergies

Modulating Shrimp Tropomyosin-Mediated Allergy: Hypoallergen DNA Vaccines Induce Regulatory T Cells to Reduce Hypersensitivity in Mouse Model

Allergens are not pathogens

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