Novel Amb a 1 CpG Oligodeoxyribonucleotide Conjugate Ragweed Vaccine Administered to Children

Nayak, Apurva; Tripathy, Ita; Levitt, Dan

doi:10.1016/j.jaci.2005.12.635

Cited by 6 publications

(5 citation statements)

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“…Despite the promising results with AIC in the clinic, AIC failed to reduce nasal symptoms of AR patients in initial clinical trials [129] and there remains controversy regarding the onset and duration of its efficacy [127,129]. Furthermore, it failed to reduce asthma symptoms in treated children [130]. No significant local or systemic side effects related to AIC have so far been reported (fig.…”

Section: Tlr9: Sensor Of Bacterial Dnamentioning

confidence: 99%

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

Aryan

Holgate

Radzioch

et al. 2014

Int Arch Allergy Immunol

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Toll-like receptors (TLR) belong to a large family of pattern recognition receptors known as the ancient ‘gatekeepers' of the immune system. TLRs are located at the first line of defense against invading pathogens as well as aeroallergens, making them interesting targets to modulate the natural history of respiratory allergy. Agonists of TLRs have been widely employed in therapeutic or prophylactic preparations useful for asthma/allergic rhinitis (AR) patients. MPL® (a TLR4 agonist) and the CpG oligodeoxynucleotide of 1018 ISS, a TLR9 agonist, show strong immunogenicity effects that make them appropriate adjuvants for allergy vaccines. Targeting the TLRs can enhance the efficacy of specific allergen immunotherapy, currently the only available ‘curative' treatment for respiratory allergies. In addition, intranasal administration of AZD8848 (a TLR7 agonist) and VTX-1463 (a TLR8 agonist) as stand-alone therapeutics have revealed efficacy in the relief of the symptoms of AR patients. No anaphylaxis has been so far reported with such compounds targeting TLRs, with the most common adverse effects being transient and local irritation (e.g. redness, swelling and pruritus). Many other compounds that target TLRs have been found to suppress airway inflammation, eosinophilia and airway hyper-responsiveness in various animal models of allergic inflammation. Indeed, in the future a wide variability of TLR agonists and even antagonists that exhibit anti-asthma/AR effects are likely to emerge.

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Section: Tlr9: Sensor Of Bacterial Dnamentioning

confidence: 99%

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

Aryan

Holgate

Radzioch

et al. 2014

Int Arch Allergy Immunol

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“… 88 This has been attempted by an immunostimulatory conjugate of the ragweed major allergen, Amb a 1, and an oligodeoxyribonucleotide DNA sequence containing a CpG motif. Favorable redirection of the immunoreaction has been shown, 89 – 94 in addition to a reduction of symptoms and an improvement in quality of life for up to two consecutive seasons, following a regime containing only six injections in a pilot clinical trial. 95 However, further treatments were not able to prove clinical benefit, and there are currently no new data on this approach.…”

Section: Future Perspectivesmentioning

confidence: 99%

Ragweed-induced allergic rhinoconjunctivitis: current and emerging treatment options

Ihler

Canis

2015

JAA

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Ragweed (Ambrosia spp.) is an annually flowering plant whose pollen bears high allergenic potential. Ragweed-induced allergic rhinoconjunctivitis has long been seen as a major immunologic condition in Northern America with high exposure and sensitization rates in the general population. The invasive occurrence of ragweed (A. artemisiifolia) poses an increasing challenge to public health in Europe and Asia as well. Possible explanations for its worldwide spread are climate change and urbanization, as well as pollen transport over long distances by globalized traffic and winds. Due to the increasing disease burden worldwide, and to the lack of a current and comprehensive overview, this study aims to review the current and emerging treatment options for ragweed-induced rhinoconjunctivitis. Sound clinical evidence is present for the symptomatic treatment of ragweed-induced allergic rhinoconjunctivitis with oral third-generation H1-antihistamines and leukotriene antagonists. The topical application of glucocorticoids has also been efficient in randomized controlled clinical trials. Combined approaches employing multiple agents are common. The mainstay of causal treatment to date, especially in Northern America, is subcutaneous immunotherapy with the focus on the major allergen, Amb a 1. Beyond this, growing evidence from several geographical regions documents the benefit of sublingual immunotherapy. Future treatment options promise more specific symptomatic treatment and fewer side effects during causal therapy. Novel antihistamines for symptomatic treatment are aimed at the histamine H3-receptor. New adjuvants with toll-like receptor 4 activity or the application of the monoclonal anti-immunoglobulin E antibody, omalizumab, are supposed to enhance conventional immunotherapy. An approach targeting toll-like receptor 9 by synthetic cytosine phosphate–guanosine oligodeoxynucleotides promises a new treatment paradigm that aims to modulate the immune response, but it has yet to be proven in clinical trials.

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“…The Dynavax product has been evaluated in a small pilot study in children. 37 In this placebo-controlled pilot study evaluating 6-to 17-year old patients with ragweed PAR, three dose escalation cohorts (six patients each), and one placebo cohort (six patients) were examined. The same six weekly dosing schedule as adults was used.…”

Section: Investigational Immune Modulationmentioning

confidence: 99%

Pediatric allergic rhinitis: Current and future state of the art

Carr

2008

allergy asthma proc

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Allergic rhinitis (AR) is the most common cause of allergic disease in the pediatric population. This chronic condition impacts quality of life, exacerbates comorbid conditions, and results in a significant economic burden. With an accurate diagnosis, there are many available therapies to reduce the burden of AR. Options include allergen avoidance, pharmacotherapy, and immune modulation. This review provides a comprehensive discussion of the current and future state of the art in the treatment of pediatric AR.

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Novel Amb a 1 CpG Oligodeoxyribonucleotide Conjugate Ragweed Vaccine Administered to Children

Cited by 6 publications

References 0 publications

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

Ragweed-induced allergic rhinoconjunctivitis: current and emerging treatment options

Pediatric allergic rhinitis: Current and future state of the art

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