Use of A‐type CpG oligodeoxynucleotides as an adjuvant in allergen‐specific immunotherapy in humans: a phase I/IIa clinical trial

Senti, Gabriela; Johansen, Pål; Haug, Susanne; Bull, Carroll G.; Gottschaller, C.; Müller, P; Pfister, Th.; Maurer, Patrik; Bachmann, Martin F.; Graf, Nicole; Kündig, Thomas M.

doi:10.1111/j.1365-2222.2008.03191.x

Cited by 199 publications

(170 citation statements)

References 51 publications

(59 reference statements)

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“…In that study, CpG‐ODN was packed in virus‐like particles as adjuvants, and administered subcutaneously with house dust mite allergens, which led to a clinical remission of at least 38 weeks 6.…”

Section: Discussionmentioning

confidence: 99%

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

Klier

Geis

Steuer

et al. 2017

Immunity Inflam & Disease

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IntroductionNew therapeutic strategies to modulate the immune response of human and equine allergic asthma are still under extensive investigation. Immunomodulating agents stimulating T‐regulatory cells offer new treatment options beyond conventional symptomatic treatment or specific immunotherapy for human and equine allergic airway diseases, with the goal of a homoeostatic T‐helper cell balance. The aim of this study was to evaluate the effects of a nebulized gelatin nanoparticle‐CpG formulation (CpG‐GNP) with and without specific allergens for the treatment of spontaneous allergic equine asthma as a model for human asthma.MethodsTwenty equine asthma‐affected horses were treated either with CpG‐GNP alone or CpG‐GNP with allergens. Two specific allergens were selected for each horse based on history and an in‐vitro test. Each horse received seven administrations of the respective nebulized composition and was examined before treatment, immediately after and 6 weeks after the treatment course.ResultsClinical parameters such as breathing rate, indirect interpleural measurement, arterial blood gases, amount of tracheal mucus and percentage of neutrophils and cytokines in tracheal washes and serum samples were evaluated. Treatment with CpG‐GNP alone as well as in combinations with relevant allergens resulted in clinical improvement of nasal discharge, breathing rate, amount of secretion and viscosity, neutrophil percentage and partial oxygen pressure directly after and 6 weeks after treatment. There were no significant differences between the two treatments in clinical parameters or local cytokine profiles in the tracheal wash fluid (IL‐10, IFN‐g, and IL‐17). IL‐4 concentrations decreased significantly in both groups.ConclusionNonspecific CpG‐GNP‐based immunotherapy shows potential as a treatment for equine and possibly also human allergic asthma.

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Section: Discussionmentioning

confidence: 99%

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

Klier

Geis

Steuer

et al. 2017

Immunity Inflam & Disease

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“…In other studies in which CpGs were deployed, for example in a study on asthma in humans,20 and a study on dogs with atopic dermatitis,21 CpGs were used as adjuvants for an allergen‐specific immunotherapy or as vaccine adjuvants for increased effectiveness of the human hepatitis B11 and the equine influenza and Rhodococcus equi vaccines 22, 23, 24, 25. In these studies, the CpGs induced a strong Th1 cell‐mediated and humoral immune response 11.…”

Section: Discussionmentioning

confidence: 99%

“…As an adjuvant, CpG‐ODN has been successfully used both in a human phase I and IIa in vivo asthma study with the house dust mite allergen as well as in a study of atopic dogs with specific allergens as an allergen‐specific immunotherapy 20, 21. CpG‐ODN also has been applied as an adjuvant in in vitro and in vivo vaccination studies 22, 23, 24, 25.…”

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confidence: 99%

Nanoparticulate CpG Immunotherapy in RAO‐Affected Horses: Phase I and IIa Study

Klier

Lehmann

Fuchs

et al. 2015

Veterinary Internal Medicne

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BackgroundRecurrent airway obstruction (RAO), an asthma‐like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine‐phosphate‐guanosine‐oligodeoxynucleotides (CpG‐ODN) are known to direct the immune system toward a Th1‐pathway, and away from the pro‐allergic Th2‐line (Th2/Th1‐shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG‐ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP‐bound CpG‐ODN in RAO‐affected horses have shown promising results.ObjectivesThe aim of this study was to evaluate the clinical and immunological effects of GNP‐bound CpG‐ODN in a double‐blinded, placebo‐controlled, prospective, randomized clinical trial and to verify a sustained effect post‐treatment.Animals and MethodsTwenty‐four RAO‐affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post‐treatment (III).ResultsAt time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO 2 and neutrophil percentage, and an increase in arterial oxygen pressure.Conclusion and Clinical ImportanceAdministration of a GNP‐bound CpG‐ODN formulation caused a potent and persistent effect on allergic and inflammatory‐induced clinical variables in RAO‐affected horses. This treatment, therefore, provides an innovative, promising, and well‐tolerated strategy beyond conventional symptomatic long‐term therapy and could serve as a model for asthma treatment in humans.

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“…Other VLPs displaying various TLR ligands have provided encouraging results in various pathological settings. In particular, VLPs loaded with CpG oligodeoxynucleotides (TLR9 ligands) have shown a very promising therapeutic potential against cancer (57,58) but also in other context such as allergen-specific immunotherapy (59)(60)(61). Cancer immunotherapy with DC-based vaccines also has provided great promises in the past few years but requires optimization to become fully effective (62,63).…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Lebel

Daudelin

Chartrand

et al. 2014

The Journal of Immunology

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Developing new adjuvants and vaccination strategies is of paramount importance to successfully fight against many life-threatening infectious diseases and cancer. Very few adjuvants are currently authorized for human use, and these mainly stimulate a humoral response. However, specific Abs are not sufficient to confer protection against persisting infections or cancer. Therefore, development of adjuvants and immunomodulators able to enhance cell-mediated immune responses represents a major medical need. We recently showed that papaya mosaic virus nanoparticles (PapMV), self-assembled from the coat protein of a plant virus and a noncoding ssRNA molecule, are highly immunogenic in mice. PapMV can be used either as a vaccine delivery platform, through fusion of various epitopes to the coat protein or as adjuvant to enhance humoral immune responses against coadministered Ags or vaccines. However, the mechanisms that confer these immunomodulatory properties to PapMV and its ability to enhance T cell vaccines remain unknown. Using immunization studies in mice, we demonstrate in this paper that PapMV represents a novel TLR7 agonist with strong immunostimulatory properties. More importantly, pretreatment with PapMV significantly improves effector and memory CD8+ T cell responses generated through dendritic cell vaccination increasing protection against a Listeria monocytogenes challenge.

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Use of A‐type CpG oligodeoxynucleotides as an adjuvant in allergen‐specific immunotherapy in humans: a phase I/IIa clinical trial

Cited by 199 publications

References 51 publications

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

Nanoparticulate CpG Immunotherapy in RAO‐Affected Horses: Phase I and IIa Study

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

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