New routes for allergen immunotherapy

Johansen, Pål; Moos, Seraina von; Mohanan, Deepa; Kündig, Thomas M.; Senti, Gabriela

doi:10.4161/hv.21948

Cited by 32 publications

(18 citation statements)

References 133 publications

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“…However, rational designs for alternative therapies must consider the neglected natural routes, the mucosal routes. 108 Several delivery systems such as polymeric nanoparticles have been developed for mucosal routes with very promising results. 109 Yet these systems are still a long way from being authorized.…”

Section: Adjuvant Limitationsmentioning

confidence: 99%

Adjuvants for allergy immunotherapeutics

Gamazo

D'Amelio

Gastaminza

et al. 2017

Human Vaccines & Immunotherapeutics

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Allergic diseases are reaching epidemic proportions in developed countries. In particular, food allergy is increasing in prevalence and severity, thus becoming an important socioeconomic burden. Numerous cell types and cell populations, which form an intricate and balanced network, are involved in an immune response. This balance is occasionally disturbed, leading to the onset of different diseases, such as allergic diseases. Antihistamines and corticosteroids provide some degree of relief from the symptoms of allergic conditions. However, the only treatment that can revert the disease is immunotherapy. Nevertheless, specific immunotherapy has at least 2 major drawbacks: it is time-consuming, and it can produce local and even systemic allergic side effects. Immunotherapy's potential goes beyond our current knowledge of the immune response; nevertheless, we can still design strategies to reach a safer immune modulation for treating allergies. This review deals with the use of adjuvants to reduce the undesirable side effects associated with specific allergen immunotherapy. For example, nanoparticles used as immunoadjuvants are offering promising results in preclinical assays.

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Section: Adjuvant Limitationsmentioning

confidence: 99%

Adjuvants for allergy immunotherapeutics

Gamazo

D'Amelio

Gastaminza

et al. 2017

Human Vaccines & Immunotherapeutics

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“…Moreover, ILIT increased production of IL-2, IFN-γ, IL-4, and IL-10 when compared with subcutaneous allergen-specific immunotherapy, suggesting that ILIT does not polarize the response toward T H 1, T H 2, or Treg cells but rather generates an overall stronger response. 6,7 …”

mentioning

confidence: 99%

Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production

Majewska‐Szczepanik

Askenase

Lobo

et al. 2016

Journal of Allergy and Clinical Immunology

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Background Subcutaneous allergen-specific immunotherapy is a standard route for the immunotherapy of allergic diseases. It modulates the course of allergy and can generate long-term remission. However, subcutaneous allergen-specific immunotherapy can also induce anaphylaxis in some patients, and therefore additional routes of administration should be investigated to improve the safety and tolerability of immunotherapy. Objective We sought to determine whether epicutaneous treatment with antigen in the presence of a Toll-like receptor 9 agonist can suppress TH2-mediated responses in an antigen-specific manner. Methods Epicutaneous immunization was performed by applying a skin patch soaked with ovalbumin (OVA) plus CpG, and its suppressor activity was determined by using the mouse model of atopic dermatitis. Finally, adoptive cell transfers were implemented to characterize the regulatory cells that are induced by epicutaneous immunization. Results Epicutaneous immunization with OVA and CpG reduces the production of OVA-specific IgE and increases the synthesis of OVA-specific IgG2a antibodies in an antigen-specific manner. Moreover, eosinophil peroxidase activity in the skin and production of IL-4, IL-5, IL-10, and IL-13 are suppressed. The observed reduction of IgE synthesis is transferable with T-cell receptor (TCR) αβ+CD4+CD25− cells, whereas IgG2a production is dependent on both TCRαβ+ and TCRγδ+ T cells. Further experiments show that the described phenomenon is myeloid differentiation primary response 88, IFN-γ, and IL-17A dependent. Finally, the results suggest that epicutaneous immunization with OVA and CpG decreases the synthesis of OVA-specific IgE and skin eosinophil peroxidase activity in mice with ongoing skin allergy. Conclusion Epicutaneous application of protein antigen in the presence of adjuvant could be an attractive needle-free and self-administered immunotherapy for allergic diseases.

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“…The method of intralymphatic immunization is particularly interesting for administration of antigens that are weakly immunogenic when administrated by conventional methods such as intramuscular or subcutaneous routes. Intralymphatic vaccination has been performed with mRNA, plasmid DNA, peptides, proteins, virus and bacteria 22,[25][26][27] . While peptides and proteins have no in-build adjuvants, mRNA plasmid DNA virus and bacteria exert intrinsic adjuvant effects by providing danger signals (replicating virus and bacteria) or by stimulating Toll-like receptors (TLRs) which can sense pathogen associated molecular patterns (PAMPs) such as single-stranded RNA (TLR7 and TLR8), double stranded RNA (TLR3), un-methylated cytosine and guanine oligonucleotide clusters (TLR9), bacterial flaggelin (TLR5), lipopolysaccharide (TLR2 and 4) as well as other viral and bacterial molecules 28 .…”

Section: Discussionmentioning

confidence: 99%

Intralymphatic Immunotherapy and Vaccination in Mice

Johansen

Kündig

2014

JoVE

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Vaccines are typically injected subcutaneously or intramuscularly for stimulation of immune responses. The success of this requires efficient drainage of vaccine to lymph nodes where antigen presenting cells can interact with lymphocytes for generation of the wanted immune responses. The strength and the type of immune responses induced also depend on the density or frequency of interactions as well as the microenvironment, especially the content of cytokines. As only a minute fraction of peripherally injected vaccines reaches the lymph nodes, vaccinations of mice and humans were performed by direct injection of vaccine into inguinal lymph nodes, i.e. intralymphatic injection. In man, the procedure is guided by ultrasound. In mice, a small (5-10 mm) incision is made in the inguinal region of anesthetized animals, the lymph node is localized and immobilized with forceps, and a volume of 10-20 μl of the vaccine is injected under visual control. The incision is closed with a single stitch using surgical sutures. Mice were vaccinated with plasmid DNA, RNA, peptide, protein, particles, and bacteria as well as adjuvants, and strong improvement of immune responses against all type of vaccines was observed. The intralymphatic method of vaccination is especially appropriate in situations where conventional vaccination produces insufficient immunity or where the amount of available vaccine is limited.

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New routes for allergen immunotherapy

Cited by 32 publications

References 133 publications

Adjuvants for allergy immunotherapeutics

Adjuvants for allergy immunotherapeutics

Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production

Intralymphatic Immunotherapy and Vaccination in Mice

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