Research Activities
Allergen and T-Cell Reagent Resources for the Study of Allergic Diseases
The National Institute of Allergy and Infectious Diseases (NIAID) developed this new program in response to a 2005 NIAID-sponsored workshop on the future of immunotherapy. The subject matter experts who attended the workshop recognized a great need to identify and characterize allergen-specific T-cell epitopes for use in the development of novel immune-based therapeutics, including those that may induce immune tolerance against clinically important allergens. The goal of this program is to identify and characterize novel allergen-specific T-cell epitopes that activate both effector and regulatory T-cell subsets. We expect that this initiative will contribute significantly to our understanding of the mechanisms that underlie allergic disease and will lead to the development of new peptide-based immunotherapies. Epitopes identified by the investigators supported through this 2007 funding initiative will be deposited in the publicly accessible NIAID Immune Epitope Database and Analysis Resource. For more information, please contact Dr. Michael Minnicozzi.
Asthma and Allergic Diseases Cooperative Research Centers
NIAID established the first Asthma and Allergic Diseases Centers in 1971, and the program is now in its fourth decade of continuous funding. The Asthma and Allergic Diseases Cooperative Research Centers have been responsible for many important basic science discoveries and clinical advances in the fields of asthma and allergy and have trained many of today’s academic leaders in these fields. The program currently supports 15 Centers located throughout the United States. These Centers conduct basic and clinical research on the mechanisms, diagnosis, treatment, and prevention of asthma and allergic diseases. Several of the Centers are preparing to launch clinical studies, including the study of anti-IgE on airway responsiveness to allergen challenge, interaction of endotoxin- and allergen-induced inflammation on airway physiology, penicillin desensitization and its effects on mast cells, the interaction between allergen-induced chronic hyperplastic eosinophilic airway disease and asthma, the effect of nasal provocation with atmospheric particulate matter on allergic sensitization, and the use of oral immunotherapy to treat cow’s milk allergy. For more information, please contact Dr. Gang Dong.
Consortium of Food Allergy Research
NIAID established this program in 2005 to study the natural history of food allergy and develop new approaches to treat and prevent food allergies. The Consortium is currently conducting an observational study in young children at high risk of developing peanut allergy. This study will correlate biologic markers and immunologic changes associated with the development of peanut allergy and the resolution of egg and cow’s milk allergy. Another study is evaluating the capacity of oral egg administration, in egg-allergic children, to induce immune tolerance to this food. The Consortium is also developing a clinical trial of sublingual immunotherapy for peanut allergy, as well as a “first-in-man” mucosal immunotherapy clinical trial that will attempt to induce T-cell tolerance in peanut-allergic subjects using recombinant and genetically modified peanut allergen proteins, administered rectally within killed E. coli. For more information, please contact Dr. Marshall Plaut.
Exploratory Investigations in Food Allergy
Co-sponsored by NIAID, the Food Allergy and Anaphylaxis Network, the Food Allergy Project, and the U.S. Environmental Protection Agency, this initiative will support innovative exploratory and developmental research on the mechanisms of food allergy and associated co-morbid conditions, including atopic dermatitis, asthma, and eosinophilic gastroenteritis, using ex vivo specimens from human subjects or animal models of food allergy. One important goal of this initiative is to attract additional investigators to the field of food allergy research. NIAID expects to award grants under this initiative in mid-2008. For more information, please contact Dr. Richard Sawyer.
Atopic Dermatitis and Vaccinia Immunization Network (ADVN)
NIAID established the ADVN in 2004 with the goal of reducing the risk of eczema vaccinatum, a potentially life-threatening complication of immunization with smallpox vaccine. Eczema vaccinatum occurs almost exclusively in persons with atopic dermatitis (AD). Smallpox vaccination in the United States was halted in 1972 due to the eradication of smallpox, but the ADVN was launched because of the potential use of smallpox as an agent of bioterrorism and the possibility of vaccinating large numbers of people with vaccinia. The ADVN includes both clinical studies and studies in mouse models of AD. ADVN investigators have shown that subjects with AD have diminished cutaneous innate immune responses. Moreover, subsets of AD patients with a history of eczema herpeticum have been found to have a more profound defect in their capacity to mount an innate immune response. Lessons learned from studies of patients with eczema herpeticum are expected to provide important information about the risk of eczema vaccinatum in persons with AD. For more information, please contact Dr. Marshall Plaut.
Inner-City Asthma Consortium (ICAC)
Since 1991, NIAID has funded research on asthma in inner-city areas with the goal of improving the treatment of children living in environments where the prevalence and severity of asthma is particularly high. The current program, recompeted in FY2002, consists of 10 academic clinical centers, an administrative center, and a statistical and data coordinating center. The goals of the ICAC are to evaluate the safety and efficacy of promising immune-based therapies to reduce the severity of asthma and prevent disease onset, to investigate the mechanisms of action of immune-based therapies developed to treat this disease, as well as to develop diagnostic and prognostic biomarkers. Recently completed and ongoing clinical studies include: 1) evaluation of the use of exhaled nitric oxide as a biomarker to supplement a guidelines-based approach to the management of children with asthma; 2) a clinical trial of the effectiveness of anti-IgE therapy in asthmatic children; 3) a Phase I study of sublingual cockroach immunotherapy; and 4) a birth cohort study of children at high risk of developing asthma with the goal of identifying immunologic characteristics that will predict the development and the severity of asthma at a later age. For more information, please contact Dr. Peter Gergen.
Immune Tolerance Network (ITN)
First funded in 1999 and renewed in 2007, the ITN is an international consortium of investigators in the United States, Canada, Europe, and Australia dedicated to the development and evaluation of novel, tolerance-inducing therapies in immune-mediated disorders, including asthma and allergic disease. The ITN recently completed a proof-of-principle clinical trial using a recombinant ragweed allergen chemically conjugated to immunostimulatory DNA to treat allergic rhinitis (Creticos et al., 2006). Just six injections of this allergen-DNA conjugate, given to ragweed allergic patients prior to seasonal exposure to ragweed pollen, markedly reduced rhinitis symptoms during both that year’s and the following year’s ragweed season. An ongoing ITN clinical trial is testing whether regular consumption of a peanut snack by high-risk children enrolled between four and ten months of age will prevent the later development of peanut allergy. For more information, please contact Dr. Marshall Plaut.
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