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Article ; Online: Influence of antigen density and TLR ligands on preclinical efficacy of a VLP‐based vaccine against peanut allergy

Krenger, Pascal S. / Josi, Romano / Sobczak, Jan / Velazquez, Thalia L. C. / Balke, Ina / Skinner, Murray A. / Kramer, Matthias F. / Scott, Callum J. W. / Hewings, Simon / Heath, Matthew D. / Zeltins, Andris / Bachmann, Martin F.

Allergy. 2024 Jan., v. 79, no. 1, p. 184-199

2024 , Page(s) 184–199

Abstract: BACKGROUND: Virus‐like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT‐VLPs) that are genetically fused with one of the ...

Abstract	BACKGROUND: Virus‐like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT‐VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMVTT‐Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut‐based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP‐compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development. METHOD: The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS‐PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut. RESULTS: A TLR 7 dependent formation of Ara h 2 specific high‐avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen‐specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut‐derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity. CONCLUSIONS: Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting.
Keywords	RNA ; active pharmaceutical ingredients ; allergens ; animal models ; clinical trials ; cucumbers ; humans ; hypersensitivity ; immunogenicity ; ligands ; mass spectrometry ; mice ; peanuts ; polyacrylamide gel electrophoresis ; vaccination ; vaccine development ; vaccines
Language	English
Dates of publication	2024-01
Size	p. 184-199
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15897
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Peripheral blood mononuclear cell transcriptome profile in a clinical trial with subcutaneous, grass pollen allergoid immunotherapy.

Starchenka, Sviatlana / Oluwayi, Kemi / Heath, Matthew / Armfield, Oliver / Shamji, Mohamed / Layhadi, Janice / Lis, Katarzyna / Cadavez, Lisa / Rusyn, Olesya / Skinner, Murray / De Kam, Pieter-Jan

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

2024 Volume 54, Issue 2, Page(s) 130–142

Abstract: Introduction: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment in allergic airway diseases. Underlying immunological mechanisms and candidate biomarkers, which may be translated into predictive/surrogate measures of clinical ...

Abstract	Introduction: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment in allergic airway diseases. Underlying immunological mechanisms and candidate biomarkers, which may be translated into predictive/surrogate measures of clinical efficacy, remain an active area of research. The aim of this study was to evaluate Pollinex Quattro (PQ) Grass AIT induced immunomodulatory mechanisms, based on transcriptome profiling of peripheral blood mononuclear cells. Methods: 119 subjects with grass pollen induced seasonal allergic rhinitis (SAR) were randomized in a 2:2:1:1 ratio to receive a cumulative dose of PQ Grass as a conventional or extended pre-seasonal regimen, placebo, or placebo with MicroCrystalline Tyrosine. Gene expression analysis was an exploratory endpoint evaluated in a subgroup of 30 subjects randomly selected from the four treatment arms. Samples were collected at three time points: screening (baseline), before the start of the grass pollen season and at the end of the season. This study was funded by the manufacturer of PQ. Results: Transcriptome analysis demonstrated that the most significant changes in gene expression, for both treatment regimens, were at the end of the grass pollen season, with the main Th1 candidate molecules (IL-12A, IFNγ) upregulated and Th2 signature cytokines downregulated (IL-4, IL-13, IL-9) (p < .05). Canonical pathways analysis demonstrated Th1, Th2, Th17 and IL-17 as the most significantly enriched pathways based on absolute value of activation z-score (IzI score ≥ 2, p < .05). Upstream regulator analysis showed pronounced inhibition of pro-inflammatory allergic molecules IgE, IL-17A, IL-17F, IL-25 (IL-17E) (IzI score ≥ 2, FDR < 0.05) and activation of pro-tolerogenic molecules IL-12A, IL-27, IL-35 (EBI3) at the end of the grass pollen season. Conclusion: Peripheral blood mononuclear cells transcriptome profile showed an inhibition of Th2, Th17 pro-inflammatory allergic responses and immune deviation towards Th1 responses. PQ Grass extended regimen exhibited a superior mechanistic efficacy profile in comparison with PQ conventional regimen.
MeSH term(s)	Humans ; Allergoids ; Allergens ; Transcriptome ; Leukocytes, Mononuclear ; Pollen ; Poaceae/genetics ; Desensitization, Immunologic
Chemical Substances	Allergoids ; Allergens
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645204-8
ISSN	1365-2222 ; 0954-7894 ; 0960-2178
ISSN (online)	1365-2222
ISSN	0954-7894 ; 0960-2178
DOI	10.1111/cea.14432
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Article ; Online: In situ delivery of nanoparticles formulated with micron-sized crystals protects from murine melanoma.

Mohsen, Mona O / Heath, Matthew / Kramer, Matthias F / Velazquez, Thalia Carreno / Bullimore, Alan / Skinner, Murray A / Speiser, Daniel E / Bachmann, Martin F

Journal for immunotherapy of cancer

2022 Volume 10, Issue 9

Abstract: Introduction: Intratumoral injections of novel therapeutics can activate tumor antigen-specific T cells for locoregional tumor control and may even induce durable systemic protection (against distant metastases) via recirculating T cells. Here we ... ...

Abstract	Introduction: Intratumoral injections of novel therapeutics can activate tumor antigen-specific T cells for locoregional tumor control and may even induce durable systemic protection (against distant metastases) via recirculating T cells. Here we explored the possibility of a universal immunotherapy that promotes T-cell responses in situ and beyond, upon intratumoral injection of nanoparticles formulated with micron-sized crystals. Methods: Cucumber mosaic virus-like particles containing a tetanus toxin peptide (CuMV Results: MCT crystals were successfully decorated with CuMV Conclusions: Our new immune-enhancer turned immunologically cold tumors into hot ones and inhibited local and distant tumor growth. This type of immunotherapy does not require the identification of (patient-individual) relevant tumor antigens. It is well tolerated, non-infectious, and affordable, and can readily be upscaled for future clinical testing and broad application in melanoma and likely other solid tumors.
MeSH term(s)	Animals ; Antigens, Neoplasm ; Humans ; Immunotherapy ; Melanoma/drug therapy ; Mice ; Nanoparticles ; Tetanus Toxin ; Tumor Microenvironment
Chemical Substances	Antigens, Neoplasm ; Tetanus Toxin
Language	English
Publishing date	2022-09-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2022-004643
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Article ; Online: Safety Evaluation of PQ Birch Allergy Immunotherapy to Support Product Development.

Baldrick, Paul / Hutchings, James W / Heath, Matthew D / Skinner, Murray A

Regulatory toxicology and pharmacology : RTP

2019 Volume 108, Page(s) 104441

Abstract: PQ Birch represents an allergen-specific immunotherapy for the treatment of birch pollinosis. It consists of native birch pollen extract chemically modified with glutaldehyde adsorbed to L-tyrosine in its microcrystalline form with addition of the ... ...

Abstract	PQ Birch represents an allergen-specific immunotherapy for the treatment of birch pollinosis. It consists of native birch pollen extract chemically modified with glutaldehyde adsorbed to L-tyrosine in its microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL®). A nonclinical safety testing strategy was designed based upon interpretation of current legislation and regulatory intelligence and comprised genotoxicity studies (bacterial reverse mutation and Chinese hamster ovary micronucleus assays), a rat repeat dose toxicology study and a rabbit local tolerance study. No safety findings of concern were found. Thus, no evidence of genotoxicity was found. Relatively minor, immunostimulatory effects were seen following repeated subcutaneous dosing (once every 2 weeks for 13 weeks) as reversible increased white cell count (notably neutrophils), increased globulin level (resulting in decreased albumin/globulin [A/G] ratio) and increased fibrinogen, as well as minor dose site reaction in the form of inflammatory cell infiltrate. These findings are likely due to the immunostimulatory nature of MPL® and/or the presence of L-tyrosine within the adjuvanted vaccine. Similar dose site inflammatory changes to the injected formulation were also noted in the rabbit local tolerance study.
MeSH term(s)	Adjuvants, Immunologic/toxicity ; Animals ; Betula/immunology ; CHO Cells ; Cricetulus ; Female ; Immunotherapy/adverse effects ; Lipid A/analogs & derivatives ; Lipid A/toxicity ; Male ; Mutagenicity Tests ; Pollen/immunology ; Rabbits ; Rats, Wistar ; Rhinitis, Allergic, Seasonal/therapy ; Salmonella typhimurium/drug effects ; Salmonella typhimurium/growth & development ; Skin/drug effects ; Tyrosine/toxicity
Chemical Substances	Adjuvants, Immunologic ; Lipid A ; Tyrosine (42HK56048U) ; monophosphoryl lipid A (MWC0ET1L2P)
Language	English
Publishing date	2019-08-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604672-1
ISSN	1096-0295 ; 0273-2300
ISSN (online)	1096-0295
ISSN	0273-2300
DOI	10.1016/j.yrtph.2019.104441
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Zs.A 1711: Show issues

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Article ; Online: Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.

Krenger, Pascal S / Josi, Romano / Sobczak, Jan / Velazquez, Thalia L C / Balke, Ina / Skinner, Murray A / Kramer, Matthias F / Scott, Callum J W / Hewings, Simon / Heath, Matthew D / Zeltins, Andris / Bachmann, Martin F

Allergy

2023 Volume 79, Issue 1, Page(s) 184–199

Abstract: Background: Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMV: Method: The role of prokaryotic RNA ... ...

Abstract	Background: Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMV Method: The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut. Results: A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity. Conclusions: Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting.
MeSH term(s)	Humans ; Animals ; Mice ; Peanut Hypersensitivity/prevention & control ; Vaccines, Virus-Like Particle ; Toll-Like Receptor 7 ; Allergens ; Arachis ; Immunoglobulin G ; RNA ; Antigens, Plant
Chemical Substances	Vaccines, Virus-Like Particle ; Toll-Like Receptor 7 ; Allergens ; Immunoglobulin G ; RNA (63231-63-0) ; Antigens, Plant
Language	English
Publishing date	2023-10-10
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15897
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Article: Transcriptome analysis and safety profile of the early-phase clinical response to an adjuvanted grass allergoid immunotherapy.

Starchenka, Sviatlana / Heath, Matthew D / Lineberry, Alyson / Higenbottam, Tim / Skinner, Murray A

The World Allergy Organization journal

2019 Volume 12, Issue 11, Page(s) 100087

Abstract: Background: Specific immunotherapy is the only type of disease-modifying treatment, which induces rapid desensitization and long-term sustained unresponsiveness in patients with seasonal allergic rhinoconjunctivitis. The safety and tolerability of a new ...

Abstract	Background: Specific immunotherapy is the only type of disease-modifying treatment, which induces rapid desensitization and long-term sustained unresponsiveness in patients with seasonal allergic rhinoconjunctivitis. The safety and tolerability of a new cumulative dose regimen of 35600 SU Grass MATA MPL for subcutaneous immunotherapy were assessed in pre-seasonal, single-blind, placebo controlled Phase I clinical study. Underlying immunological mechanisms were explored using transcriptome analysis of peripheral blood mononuclear cells. Methods: Study subjects with a history of moderate to severe seasonal allergic rhinitis and/or conjunctivitis (SAR) due to grass ( Results: The results of the study indicated that the higher cumulative dose regimen of the immunotherapy was well-tolerated. Changes in gene expression profile were associated with early immune responses implicating innate and adaptive immune mechanisms. Pathways and mechanistic network analysis via IPA mapped differentially expressed genes onto canonical pathways related to T cell differentiation, cytokine signalling and Th1/Th2 activation pathways. The transcriptome findings of the study could be further verified in large-scale field studies in order to explore their potential as predictive markers of successful immunotherapy. Conclusions: The higher dose cumulative regime 35600 SU of Grass MATA MPL vaccine was well tolerated and safe. Molecular markers IL-27, IL-10, IL-4, TNF, IFNγ, TGFβ and TLR4 were the main predicted molecular drivers of the observed gene expression changes following early stages of SIT with Grass MATA MPL immunotherapy.
Language	English
Publishing date	2019-11-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2581968-9
ISSN	1939-4551
ISSN	1939-4551
DOI	10.1016/j.waojou.2019.100087
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Article ; Online: New toxicity testing of PQ grass allergy immunotherapy to support product development.

Baldrick, Paul / Hutchings, James W / Heath, Matthew D / Skinner, Murray A / Martin, Tom / Gray, Chris

Journal of applied toxicology : JAT

2019 Volume 39, Issue 10, Page(s) 1462–1469

Abstract: PQ Grass represents an allergen-specific immunotherapy for pre-seasonal treatment of patients with seasonal allergic rhinitis (or rhinoconjunctivitis) with or without mild-to-moderate bronchial asthma. It consists of a native pollen extract for 13 grass ... ...

Abstract	PQ Grass represents an allergen-specific immunotherapy for pre-seasonal treatment of patients with seasonal allergic rhinitis (or rhinoconjunctivitis) with or without mild-to-moderate bronchial asthma. It consists of a native pollen extract for 13 grass species, chemically modified with glutaraldehyde, and adsorbed to l-tyrosine in a microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL
MeSH term(s)	Adjuvants, Immunologic/therapeutic use ; Adjuvants, Immunologic/toxicity ; Animals ; Female ; Humans ; Hypersensitivity/drug therapy ; Hypersensitivity/etiology ; Immunotherapy/adverse effects ; Immunotherapy/methods ; Male ; Models, Animal ; Poaceae/adverse effects ; Rats, Wistar
Chemical Substances	Adjuvants, Immunologic
Language	English
Publishing date	2019-06-23
Publishing country	England
Document type	Journal Article
ZDB-ID	604625-3
ISSN	1099-1263 ; 0260-437X
ISSN (online)	1099-1263
ISSN	0260-437X
DOI	10.1002/jat.3832
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Article ; Online: The next generation virus-like particle platform for the treatment of peanut allergy.

Sobczak, Jan M / Krenger, Pascal S / Storni, Federico / Mohsen, Mona O / Balke, Ina / Reseviča, Gunta / Heath, Matthew D / Carreno Velazquez, Thalia L / Kramer, Matthias F / Scott, Callum J W / Skinner, Murray A / Zeltiņš, Andris / Kündig, Thomas M / Vogel, Monique / Bachmann, Martin F

Allergy

2023 Volume 78, Issue 7, Page(s) 1980–1996

Abstract: Background: Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis ... ...

Abstract	Background: Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus-like particles (VLPs), is described here for the treatment of peanut allergy. Methods and results: VLP Peanut consists of two proteins: a capsid subunit derived from Cucumber mosaic virus engineered with a universal T-cell epitope (CuMV Conclusion: VLP Peanut can be delivered to peanut-sensitized mice without triggering allergic reactions, while remaining highly immunogenic and offering protection against all peanut allergens. In addition, vaccination ablates allergic symptoms upon allergen challenge. Moreover, the prophylactic immunization setting conferred the protection against subsequent peanut-induced anaphylaxis, showing the potential for preventive vaccination. This highlights the effectiveness of VLP Peanut as a prospective break-through immunotherapy vaccine candidate toward peanut allergy. VLP Peanut has now entered clinical development with the study PROTECT.
MeSH term(s)	Mice ; Animals ; Peanut Hypersensitivity/prevention & control ; Anaphylaxis ; Prospective Studies ; Antigens, Plant ; Allergens ; Arachis
Chemical Substances	Antigens, Plant ; Allergens
Language	English
Publishing date	2023-03-29
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15704
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Article ; Online: Venom Immunotherapy: From Proteins to Product to Patient Protection.

Feindor, Martin / Heath, Matthew D / Hewings, Simon J / Carreno Velazquez, Thalia L / Blank, Simon / Grosch, Johannes / Jakob, Thilo / Schmid-Grendelmeier, Peter / Klimek, Ludger / Golden, David B K / Skinner, Murray A / Kramer, Matthias F

Toxins

2021 Volume 13, Issue 9

Abstract: In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on ... ...

Abstract	In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil
MeSH term(s)	Allergens/chemistry ; Allergens/isolation & purification ; Animals ; Bee Venoms/immunology ; Bees/chemistry ; Desensitization, Immunologic/classification ; Desensitization, Immunologic/methods ; Desensitization, Immunologic/statistics & numerical data ; Humans ; Hypersensitivity/therapy ; Wasp Venoms/immunology ; Wasps/chemistry
Chemical Substances	Allergens ; Bee Venoms ; Wasp Venoms
Language	English
Publishing date	2021-09-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins13090616
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Article ; Online: Clinical use of adjuvants in allergen-immunotherapy.

Klimek, Ludger / Schmidt-Weber, Carsten B / Kramer, Matthias F / Skinner, Murray A / Heath, Matthew D

Expert review of clinical immunology

2017 Volume 13, Issue 6, Page(s) 599–610

Abstract: Introduction: Allergen-specific Immunotherapy (AIT) is the only available treatment aimed to tackle the underlying causes of allergy. The active components of subcutaneous vaccines traditionally consist of natural or modified allergen extracts which can ...

Abstract	Introduction: Allergen-specific Immunotherapy (AIT) is the only available treatment aimed to tackle the underlying causes of allergy. The active components of subcutaneous vaccines traditionally consist of natural or modified allergen extracts which can be combined with adjuvant platforms. In recent years new targets have been further developed in an attempt to raise the safety and efficacy profile of AIT. Areas covered: In this review, we discuss the desirable attributes of adjuvants and delivery systems from empiricism to rational design, for current and future clinical applications in AIT. Expert commentary: The introduction of novel adjuvants, in combination with active targets, has been demonstrated to reduce symptoms of AIT, increase clinical efficacy of allergy treatment and reduce the number of doses. The evolution of vaccine development for AIT is entering a phase of scientific progress that challenges dogmas. Over the past century the traditional concept of immunotherapy, entailing long-course administration of native extract preparations and first generation adjuvants, has seen evolution in the past decade from proof-of-concept to clinical development pipelines encompassing the advent of second generation adjuvants and delivery systems forming essential components of modern AIT development.
Language	English
Publishing date	2017-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2274260-8
ISSN	1744-8409 ; 1744-666X
ISSN (online)	1744-8409
ISSN	1744-666X
DOI	10.1080/1744666X.2017.1292133
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