Novel vaccines for allergen-specific immunotherapy

Akinfenwa, Oluwatoyin; Rodríguez-Domínguez, Azahara; Vrtala, Susanne; Valenta, Rudolf; Campana, Raffaela

doi:10.1097/aci.0000000000000706

Cited by 17 publications

(11 citation statements)

References 94 publications

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“…They induce a regulatory response mediated by IL-35 and IL-10, which is able to reduce the later response against to olive pollen. These data are in agreement with the idea that several authors [ 92 , 93 ] propose, i.e., the prophylactic usefulness of T-cell vaccines. Figure 2 summarizes the potential of Ole e 1-derived T cell epitopes for their use as AIT.…”

Section: Ole E 1-peptidessupporting

confidence: 92%

Peptide Allergen Immunotherapy: A New Perspective in Olive-Pollen Allergy

et al. 2021

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Allergic diseases are highly prevalent disorders, mainly in industrialized countries where they constitute a high global health problem. Allergy is defined as an immune response “shifted toward a type 2 inflammation” induced by the interaction between the antigen (allergen) and IgE antibodies bound to mast cells and basophils that induce the release of inflammatory mediators that cause the clinical symptoms. Currently, allergen-specific immunotherapy (AIT) is the only treatment able to change the course of these diseases, modifying the type 2 inflammatory response by an allergenic tolerance, where the implication of T regulatory (Treg) cells is considered essential. The pollen of the olive tree is one of the most prevalent causes of respiratory allergic diseases in Mediterranean countries, inducing mainly nasal and conjunctival symptoms, although, in areas with a high antigenic load, olive-tree pollen may cause asthma exacerbation. Classically, olive-pollen allergy treatment has been based on specific immunotherapy using whole-olive pollen extracts. Despite extracts standardization, the effectiveness of this strategy varies widely, therefore there is a need for more effective AIT approaches. One of the most attractive is the use of synthetic peptides representing the B- or T-cell epitopes of the main allergens. This review summarizes experimental evidence of several T-cell epitopes derived from the Ole e 1 sequence to modulate the response to olive pollen in vitro, associated with several possible mechanisms that these peptides could be inducing, showing their usefulness as a safe preventive tool for these complex diseases.

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Section: Ole E 1-peptidessupporting

confidence: 92%

Peptide Allergen Immunotherapy: A New Perspective in Olive-Pollen Allergy

et al. 2021

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“…To this end, the modification of allergens to reduce their reactivity with IgE, the use of safer routes of administration, and the incorporation of different adjuvants to slow allergen release and/ or stimulate a desired immune response have been considered. 7,8 In terms of safety, chemical modification of allergens (allergoids) can Methods: In a randomized, double-blind, double-dummy, placebo-controlled trial, 196 subjects received placebo or PM-HDM at 500, 1000, 3000, or 5000 mannanconjugated therapeutic units (mTU)/mL in 9-arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily.…”

Section: Introductionmentioning

confidence: 99%

“…Since Noon and Freeman's first description, 6 different ways to improve both safety and efficacy of AIT have been continuously sought. To this end, the modification of allergens to reduce their reactivity with IgE, the use of safer routes of administration, and the incorporation of different adjuvants to slow allergen release and/or stimulate a desired immune response have been considered 7,8 . In terms of safety, chemical modification of allergens (allergoids) can reduce their allergenicity while sublingual immunotherapy (SLIT) may be a safer alternative than subcutaneous immunotherapy (SCIT) 9 .…”

Section: Introductionmentioning

confidence: 99%

“…To this end, the modification of allergens to reduce their reactivity with IgE, the use of safer routes of administration, and the incorporation of different adjuvants to slow allergen release and/or stimulate a desired immune response have been considered. 7 , 8 In terms of safety, chemical modification of allergens (allergoids) can reduce their allergenicity while sublingual immunotherapy (SLIT) may be a safer alternative than subcutaneous immunotherapy (SCIT). 9 On the contrary, immunomodulatory adjuvants can promote T cells to counteract pro‐allergic Th2 responses and/or induce peripheral T cell tolerance to allergens, which is considered a key step for successful AIT.…”

Section: Introductionmentioning

confidence: 99%

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First‐in‐human phase 2 trial with mite allergoids coupled to mannan in subcutaneous and sublingual immunotherapy

Nieto

Mazón

Nieto

et al. 2022

Allergy

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Background Polymerized allergens conjugated to non‐oxidized mannan (PM‐allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM‐allergoids are readily taken up by DCs and induce Treg cells. This first‐in‐human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM‐allergoid (PM‐HDM) administered subcutaneously (SC) or sublingually (SL). Methods In a randomized, double‐blind, double‐dummy, placebo‐controlled trial, 196 subjects received placebo or PM‐HDM at 500, 1000, 3000, or 5000 mannan‐conjugated therapeutic units (mTU)/mL in 9‐arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers. Results No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups. Conclusions PM‐HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml.

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“…While the use of AIT is well-established for the treatment of human allergies, its use as preventive immunotherapy in high-risk individuals has been proposed prior to sensitization [ 15 – 17 ]. Whether preventive AIT against IBH is feasible in horses remains to be established, and might become an interesting option to decrease the high incidence of IBH in horses exported from Iceland to continental Europe.…”

Section: Introductionmentioning

confidence: 99%

First clinical expression of equine insect bite hypersensitivity is associated with co-sensitization to multiple Culicoides allergens

et al. 2021

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Background Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis in horses incited by salivary allergens from Culicoides spp. IBH does not occur in Iceland, as the causative agents are absent, however a high prevalence is seen in horses exported to Culicoides-rich environments. Aims To study the natural course of sensitization to Culicoides allergens and identify the primary sensitizing allergen(s) in horses exported from Iceland utilizing a comprehensive panel of Culicoides recombinant (r-) allergens. Method IgE microarray profiling to 27 Culicoides r-allergens was conducted on 110 serological samples from horses imported to Switzerland from Iceland that subsequently developed IBH or remained healthy. Furthermore, a longitudinal study of 31 IBH horses determined IgE profiles the summer preceding first clinical signs of IBH (TIBH-1), the summer of first clinical signs (TIBH) and the following summer (TIBH+1). In a group of Icelandic horses residing in Sweden, effects of origin (born in Iceland or Sweden) and duration of IBH (<4 years, 4–7 years, >7 years) on Culicoides-specific IgE was evaluated. Sero-positivity rates and IgE levels were compared. Results At TIBH, horses were sensitized to a median of 11 r-allergens (range = 0–21), of which nine were major allergens. This was significantly higher than TIBH-1 (3, 0–16), as well as the healthy (1, 0–14) group. There was no significant increase between TIBH and TIBH+1(12, 0–23). IBH-affected horses exported from Iceland had a significantly higher degree of sensitization than those born in Europe, while duration of IBH did not significantly affect degree of sensitization. Conclusion Significant sensitization is only detected in serum the year of first clinical signs of IBH. Horses become sensitized simultaneously to multiple Culicoides r-allergens, indicating that IgE-reactivity is due to co-sensitization rather than cross-reactivity between Culicoides allergens. Nine major first sensitizing r-allergens have been identified, which could be used for preventive allergen immunotherapy.

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Novel vaccines for allergen-specific immunotherapy

Cited by 17 publications

References 94 publications

Peptide Allergen Immunotherapy: A New Perspective in Olive-Pollen Allergy

Peptide Allergen Immunotherapy: A New Perspective in Olive-Pollen Allergy

First‐in‐human phase 2 trial with mite allergoids coupled to mannan in subcutaneous and sublingual immunotherapy

First clinical expression of equine insect bite hypersensitivity is associated with co-sensitization to multiple Culicoides allergens

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