Development of a sublingual allergy vaccine for grass pollinosis

Incorvaia, Cristoforo

doi:10.2147/dddt.s10044

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…Dose optimization was considered based on the wealth of accumulated evidence to show that the effectiveness of AIT to control symptoms of AR/rhinoconjunctivitis correlates with the cumulative dose of allergen/allergoid administered during a course of subcutaneous injections or sublingual administration. 16,[26][27][28][29][30][31][32][33] Previously, various Phase I-III studies were performed using a lower strength variant of PQ Grass of 5100 SU. This prior data included the first large-scale Phase III study (N = 1028) using a lower dose of 5100 SU conducted in the US, EU, and Canada.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, clinical development of PQ Grass has focused on further enhancing the therapeutic dose level and further improving its short‐course pre‐seasonal treatment with six injections. Dose optimization was considered based on the wealth of accumulated evidence to show that the effectiveness of AIT to control symptoms of AR/rhinoconjunctivitis correlates with the cumulative dose of allergen/allergoid administered during a course of subcutaneous injections or sublingual administration 16,26–33 . Previously, various Phase I–III studies were performed using a lower strength variant of PQ Grass of 5100 SU.…”

Section: Discussionmentioning

confidence: 99%

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Short‐course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy

Kam

Zielen

Bernstein

et al. 2023

Allergy

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BackgroundA modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid‐A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short‐course treatment of grass‐pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial.MethodsIn this exploratory, randomized, double‐blind, placebo‐controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre‐seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18–65 years) with moderate‐to‐severe SAR with or without asthma that was well‐controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ‐S) and allergen‐specific IgG4 response.ResultsThe mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ‐S for the extended regimen (mean change −0.72, p = .02). Both regimens were well‐tolerated.ConclusionsThis trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well‐tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Short‐course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy

Kam

Zielen

Bernstein

et al. 2023

Allergy

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“…SLIT. Unlike during SCIT, where allergy shots are administered through injection, during SLIT, a minute amount of allergen extract is kept under the tongue of the patient, held for 2 min and then swallowed, thus avoiding the irritation of injection (127)(128)(129). However, the doses administered during SLIT are restricted by the available concentration of the allergen extract and the volume of liquid that can be held under the tongue (129,130).…”

Section: Routes Of Administration In Aitmentioning

confidence: 99%

“…Unlike during SCIT, where allergy shots are administered through injection, during SLIT, a minute amount of allergen extract is kept under the tongue of the patient, held for 2 min and then swallowed, thus avoiding the irritation of injection (127)(128)(129). However, the doses administered during SLIT are restricted by the available concentration of the allergen extract and the volume of liquid that can be held under the tongue (129,130). during the initial 4-6 months of SLIT, the allergen extract with a low allergenic potential is administered to the patients at gradually increasing doses, followed by a constant maintenance dose administered daily for up to 3 years (115).…”

Section: Routes Of Administration In Aitmentioning

confidence: 99%

Immunotherapies in the treatment of immunoglobulin E‑mediated allergy: Challenges and scope for innovation (Review)

2022

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Immunoglobulin E (IgE)-mediated allergy or hypersensitivity reactions are generally defined as an unwanted severe symptomatic immunological reaction that occurs due to shattered or untrained peripheral tolerance of the immune system. Allergen-specific immunotherapy (AIT) is the only therapeutic strategy that can provide a longer-lasting symptomatic and clinical break from medications in IgE-mediated allergy. Immunotherapies against allergic diseases comprise a successive increasing dose of allergen, which helps in developing the immune tolerance against the allergen. AITs exerttheirspecial effectiveness directly or indirectly by modulating the regulator and effector components of the immune system. The number of success stories of AIT is still limited and it canoccasionallyhave a severe treatment-associated adverse effect on patients. Therefore, the formulation used for AIT should be appropriate and effective. The present review describes the chronological evolution of AIT, and provides a comparative account of the merits and demerits of different AITs by keeping in focus the critical guiding factors, such as sustained allergen tolerance, duration of AIT, probability of mild to severe allergic reactions and dose of allergen required to effectuate an effective AIT. The mechanisms by which regulatory T cells suppress allergen-specific effector T cells and how loss of natural tolerance against innocuous proteins induces allergy are reviewed. The present review highlights the major AIT bottlenecks and the importantregulatory requirements for standardized AIT formulations. Furthermore, the present reviewcalls attention to the problem of 'polyallergy', which is still a major challenge for AIT and the emerging concept of 'component-resolved diagnosis' (CRD) to address the issue. Finally, a prospective strategy for upgrading cRd to the next dimension is provided, and a potential technology for delivering thoroughly standardized AIT with minimal risk is discussed.

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“…Allergies are a problem that affects a significant part of the population, from young children to older adults. The most common allergen that causes airway problems is grass pollen [65,66]. This allergy frequently manifests itself with rhinitis or even asthma and is generally treated with antihistamines and corticosteroids to control the symptoms, but that does not improve the problem from the causes.…”

Section: Sublingual Delivery Of Antigens As An Alternative For Allergy Treatmentmentioning

confidence: 99%

Buccal and Sublingual Vaccines: A Review on Oral Mucosal Immunization and Delivery Systems

2021

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Currently, most vaccines available on the market are for parental use; however, this may not be the best option on several occasions. Mucosal routes of administration such as intranasal, sublingual, and buccal generate great interest due to the benefits they offer. These range from increasing patient compliance to inducing a more effective immune response than that achieved through conventional routes. Due to the activation of the common mucosal immune system, it is possible to generate an effective systemic and local immune response, which is not achieved through parenteral administration. Protection against pathogens that use mucosal entry routes is provided by an effective induction of mucosal immunity. Mucosal delivery systems are being developed, such as films and microneedles, which have proven to be effective, safe, and easy to administer. These systems have multiple advantages over commonly used injections, which are simple to manufacture, stable at room temperature, painless for the patient since they do not require puncture. Therefore, these delivery systems do not require to be administered by medical personnel; in fact, they could be self-administered.

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Development of a sublingual allergy vaccine for grass pollinosis

Cited by 9 publications

References 40 publications

Short‐course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy

Short‐course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy

Immunotherapies in the treatment of immunoglobulin E‑mediated allergy: Challenges and scope for innovation (Review)

Buccal and Sublingual Vaccines: A Review on Oral Mucosal Immunization and Delivery Systems

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