DR1 DataRelease

SDY1: Efficacy and Safety Evaluation of Allergen Immunotherapy Co-Administered with Omalizumab (an anti-IgE Monoclonal Antibody)
Status: New
Description:

Allergic rhinitis affects 20 to 40 million Americans annually. Allergy symptoms, which can range from mild to seriously debilitating, may affect quality of life. Left untreated, allergic rhinitis can exacerbate or trigger more serious conditions, such as asthma and sinus inflammation.

Individuals with allergies react to harmless particles such as dust or pollen. Proteins in the blood called IgE antibodies treat the harmless particles as invaders and trigger an immune system response. The immune response results in harmful inflammation of healthy tissues. In ragweed allergy, inflammation occurs in the airways and causes familiar allergy symptoms like sneezing, coughing, and general discomfort.

Omalizumab is an investigational drug that has been shown to block the effects of IgE antibodies. The blocking effect of omalizumab is temporary, but giving the drug to people before their regular allergy shots may make the shots more effective.

Participants in this study will be randomly assigned to receive injections of omalizumab or a placebo before an accelerated course of allergy shots (given over 12 weeks). The participants will return for follow-up for up to one year, and they may have as many as 27 study visits.

Program/Contract:
ProgramContract
ITN: Collaborative Network for Clinical Research on Immune Tolerance Network Immune Tolerance Network - Casale
DOI: 10.21430/M38Y09R3R9
Subjects: 159
Study PI, contact:
NameOrganizationSite
Thomas Casale Creighton University School of Medicine Creighton University
Publications:
Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis.. J Allergy Clin Immunol. Jan 2006. doi: b 2005 Dec 2. [Pubmed: 16387596]
Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding.. J Allergy Clin Immunol. Sep 2007. doi: b 2007 Jul 12. [Pubmed: 17631952]
Resources:
Clinicaltrials.gov http://clinicaltrials.gov/ct2/show/NCT00078195]
ImmuneTolerance.org http://www.immunetolerance.org/studies/efficacy-and-safety-evaluation-allergen-immunotherapy-co-administered-with-omalizumab-anti-i]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 4376
Flow Cytometry 14462
Clinical Assessments:
15 mins post injection allergy skin reaction measurement
24 hrs post injection allergy skin reaction measurement
Allergen History
Allergy Symptom History
Animal Exposure History
Food Allergy History
Immunotherapy History
Other Allergy History
Participant Diary Card Record
Pre-injection Measurement for Rush immunotherapy(Histamine)
Pre-injection Measurement for Rush immunotherapy(Ragweed)
Vital Signs
SDY2: Immune Response to Varicella Vaccination in Subjects with Atopic Dermatitis Compared to Nonatopic Controls
Status: New
Description: This is a mechanistic, double-aim, non-randomized study that will be conducted at 2 sites, Children's Hospital Boston and National Jewish Medical and Research Center. Study participants 12 to 36 months of age with AD and without AD will be enrolled to assess immune response after varicella vaccination.

Estimated Study Duration:

The study is scheduled to be completed in 36 months. Subjects will only complete one scheduled study visit.

Study Population:

Subjects will be enrolled over a 12 month period. Subjects will be recruited at Children's Hospital Boston and National Jewish Medical and Research Center.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3G33VVU77
Subjects: 71
Study PI, contact:
NameOrganizationSite
Lynda Schneider Children's Hospital, Boston Children's Hospital Boston
Publications:None
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00406081]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 500
ELISPOT 293
Flow Cytometry 442
Clinical Assessments:
Any Adverse Event?
Any medications taken
Atopic Dermatitis Assessment
EASI Score
Family History
Medical History
Non-AD Assessment
Physical Exam
Rajka-Langeland Score
Skin exam
Skin Infection History
SDY3: Responses to Immunization with Keyhole Limpet Hemocyanin (KLH) Administered by Scarification and the Intradermal (ID) Route
Status: New
Description: AD is characterized by skin inflammation and recurrent skin infections. In addition, people with AD may have a severe and sometimes fatal reaction to the smallpox vaccine called EV. KLH is a carrier protein that can be used to deliver antibodies to the body. However KLH itself, may cause an immune response.

The purpose of this study is to determine the body's reaction to pure KLH in people without AD. This will be used to establish a baseline immune response and may be compared to the immune response in people with AD during future studies.

This study will last 8 weeks and will have 11 study visits. Participants in this study will be randomly assigned to 1 of 4 groups. All participants will receive their immunizations at Visits 5 and 6.
  • Participants in Arm 1 will receive 2 immunizations each with 100 μg of KLH each.
  • Participants in Arm 2 will receive 2 immunizations through scarification (a shallow cut in the skin) with jabs, each containing 20 mg/mL of KLH. Adverse reactions will be monitored after each immunization. Once safety data from these 2 groups have been reviewed, the next 2 groups will be enrolled.
  • Participants in Arm 3 will receive 2 immunizations each with 250 μg of KLH each.
  • Participants in Arm 4 will receive 2 immunizations through scarification with 15 jabs, each containing 20mg/mL of KLH. Other study visits will include allergy testing and blood and urine collection.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3STULGP9K
Subjects: 26
Study PI, contact:
NameOrganizationSite
Henry Milgrom National Jewish Health National Jewish Health
Publications:
Response to cutaneous immunization with low-molecular-weight subunit keyhole limpet hemocyanin.. Int Arch Allergy Immunol. - 2012. doi: 10.1159/000328784. Epub 2011 Oct 28. [Pubmed: 22042247]
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00614731]
Assays:None
Clinical Assessments:
Any Adverse Event?
Any medications taken
DTH Test
DTH Test Assessment
Immunization KLH
Medical History
Physical Exam
SDY4: Risk Factors in Atopic Dermatitis for the Development of Eczema Herpeticum
Status: New
Description: DETAILED_DESCRIPTION

AD is characterized by skin inflammation and recurrent skin infections. In addition, people with AD may have a severe and sometimes fatal reaction to the smallpox vaccine called EV. KLH is a carrier protein that can be used to deliver antibodies to the body. However KLH itself, may cause an immune response.

The purpose of this study is to determine the body's reaction to pure KLH in people without AD. This will be used to establish a baseline immune response and may be compared to the immune response in people with AD during future studies.

This study will last 8 weeks and will have 11 study visits. Participants in this study will be randomly assigned to 1 of 4 groups. All participants will receive their immunizations at Visits 5 and 6.

  • Participants in Arm 1 will receive 2 immunizations each with 100 μg of KLH each.
  • Participants in Arm 2 will receive 2 immunizations through scarification (a shallow cut in the skin) with jabs, each containing 20 mg/mL of KLH. Adverse reactions will be monitored after each immunization. Once safety data from these 2 groups have been reviewed, the next 2 groups will be enrolled.
  • Participants in Arm 3 will receive 2 immunizations each with 250 μg of KLH each.
  • Participants in Arm 4 will receive 2 immunizations through scarification with 15 jabs, each containing 20mg/mL of KLH. Other study visits will include allergy testing and blood and urine collection.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M398H5TAXP
Subjects: 235
Study PI, contact:
NameOrganizationSite
Thomas Bieber The University of Bonn, Germany The University of Bonn, Germany
Publications:
Atopic dermo-respiratory syndrome is a correlate of eczema herpeticum.. Allergy. Jul 2011. doi: 10.1111/j.1398-9995.2010.02538.x. Epub 2011 Jan 24. [Pubmed: 21255038]
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00438022]
Assays:
Assay TypeNumber of Exp. Samples
Flow Cytometry 3500
Clinical Assessments:
AD Assessment
Any Adverse Event?
Clinical variant of AD
EASI Score
Eczema herpeticum evaluation
Family History
Medical History
Onset of AD and evolution
Physical Exam
Question about medications taken
Rajka-Langeland Score
Severity Scoring of Atopic Dermatitis
SDY5: Analysis and Correlation of Cathelicidin Expression in Skin and Saliva of Subjects with Atopic Dermatitis and Psoriasis
Status: New
Description: People with AD or psoriasis are very sensitive to skin infections and inflammations. A group of small proteins known as cathelicidins are known to be responsible for immune defense against such infections. People with AD or psoriasis seem to be missing these proteins from their skin.

The purpose of this study is to determine if the amount of cathelicidins and other small proteins in saliva is a predictor for the amount found in the skin. This is a single visit observational study. People with AD or psoriasis, as well as healthy participants, are being recruited for this study. Participants will provide a detailed medical history and undergo a physical examination. In addition, saliva and blood collection, and skin punch biopsies will be performed.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3KLK90P9T
Subjects: 85
Study PI, contact:
NameOrganizationSite
Richard Gallo University of California at San Diego University of California at San Diego
Publications:None
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00407979]
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00789880]
Assays:None
Clinical Assessments:
Any Adverse Event?
Any medications taken
Medical History
Physical Exam
Psoriasis Area and Severity Index
Rajka-Langeland Score
Skin exam
Skin lesion involved and skin lesion duration
Smoking Status
SDY6: ADVN Biomarker Registry Study
Status: New
Description: This protocol describes the development of the Atopic Dermatitis and Vaccinia Immunization Network (ADVN) Biomarker Registry Study. The proposed Registry is a database with a minimum of 1,000 subjects who have voluntarily agreed to provide medical and demographic information about themselves and their health status.

These data will be collected until a minimum of 12 weeks prior to the end of the funding cycle to allow for final data entry, query resolution, and database lock and will be used to identify potential subjects for future studies designed to improve scientific understanding of the increased risk of complications after exposure to the smallpox vaccine for people with atopic dermatitis (AD).

In addition, enrolled subjects will be asked to provide a blood sample for evaluation of biomarkers, and permission for blood sample storage to support future analyses. Provision of a blood sample for evaluation of biomarkers for future analyses will be optional for subjects under 6 years of age.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3J22ZOZM9
Subjects: 1231
Study PI, contact:
NameOrganizationSite
Lisa Beck University of Rochester Medical Center University of Rochester Medical Center
Publications:None
Resources:
NIH Reporter https://projectreporter.nih.gov/project_info_details.cfm?aid=9042233&icde=33171050]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 236
Clinical Assessments:
Affected body surface area for Atopic dermatitis subject
Allergy History
Any Adverse Event?
Any medications taken
Atopic Dermatitis Assessment
Atopic dermatitis supplemental information
CBC Panic values
Confirmation of Diagnostic Category
Current Medical History
EASI Score
Eczema Herpeticum Assessment
EV Assessment
Family History
Health Status
Initial diagnosis
Interim Medical History
Interim Skin Infection History
Medical History
Molluscum Contagiosum Assessment
Non-AD Assessment
Original Diagnosis
Physical Exam
Rajka-Langeland Score
Skin Infection History
Skin/Integument exam
Staphylococcus aureus infection history for previously enrolled subject
Staphylococcus Aureus Infection History Questionnaire
Vaccination history
SDY7: ADVN Biomarker Registry Study: CMI/Ab-Vaccinia Substudy
Status: New
Description: To measure total and specific antibody titers and T cell responses in a sample of subjects who experienced eczema vaccinatum (EV) and a group of subjects who did not suffer from EV (normal controls or healthy AD subjects).
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3G81PA5G7
Subjects: 90
Study PI, contact:
NameOrganizationSite
Donald Leung National Jewish Health National Jewish Health
Publications:None
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00550316]
Assays:None
Clinical Assessments:
Any Adverse Event?
EASI Score
Family History
Interim Medical History
Interim Skin Infection History
Medical History
Physical Exam
Question about medications taken
Rajka-Langeland Score
Skin/Integument exam
Smallpox vaccination status
Vaccination history
SDY8: ADVN Biomarker Registry Study: CMI-HSV Substudy
Status: New
Description: To evaluate AD subjects cell mediated immunity CMI responses to Herpes simplex virus.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3GCZX3F7X
Subjects: 67
Study PI, contact:
NameOrganizationSite
Donald Leung National Jewish Health National Jewish Health
Publications:None
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00550316]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 251
ELISPOT 64
Clinical Assessments:
Any Adverse Event?
EASI Score
Family History
Interim Medical History
Interim Skin Infection History
Medical History
Physical Exam
Question about medications taken
Rajka-Langeland Score
Skin Infection History
Skin/Integument exam
Vaccination history
SDY9: ADVN Biomarker Registry: Neutrophil Substudy
Status: New
Description: To evaluate the chemotactic function of peripheral blood leukocytes such as neutrophils in subjects with ADEH+, ADEH-, and NA controls.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3OP2QB064
Subjects: 62
Study PI, contact:
NameOrganizationSite
Lisa Beck University of Rochester Medical Center University of Rochester Medical Center
Publications:None
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00550316]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 64
Flow Cytometry 490
Clinical Assessments:
Any Adverse Event?
Any medications taken?
EASI Score
Family History
Interim Medical History
Interim Skin Infection History
Medical History
Physical Exam
Rajka-Langeland Score Assessment
Skin Infection History
Skin/Integument exam
Vaccination and Viral History
SDY10: Role of Antimicrobial Peptides in Host Defense Against Vaccinia Virus
Status: New
Description: AD is a chronic inflammatory skin disease characterized by frequent viral skin infections. Recent studies have found that components in the skin of people with AD may block AMP expression. AMPs are responsible for preventing infection from viruses.

The purpose of this study is to examine small pox virus replication and AMP expression in the skin of patients with AD as well as identify other antiviral molecules involved in immune response. These findings will be compared with those of people with psoriasis or asthma, or healthy individuals. This study will consist of one study visit at which skin and blood samples will be taken.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3K0GCB4KL
Subjects: 292
Study PI, contact:
NameOrganizationSite
Donald Leung National Jewish Health National Jewish Health
Publications:
Vaccinia virus-specific molecular signature in atopic dermatitis skin.. J Allergy Clin Immunol. Jan 2010. doi: 10.1016/j.jaci.2009.10.024. [Pubmed: 20109744]
The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections.. J Allergy Clin Immunol. Nov 2011. doi: 10.1016/j.jaci.2011.06.003. Epub 2011 Jul 18. [Pubmed: 21762972]
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/study/NCT00407069]
Assays:None
Clinical Assessments:
Any Adverse Event?
Any Concomitant Medications
Medical History
Physical Exam
Rajka-Langeland Score
Skin/Integument exam
SDY13: Analysis of the Response of Subjects with Atopic Dermatitis to Oral Vitamin D3 by Measurement of Antimicrobial Peptide Expression in Skin and Saliva
Status: New
Description: The goal of the Atopic Dermatitis Vaccinia Network (ADVN) is to research methods for preventing atopic dermatitis (AD) patients from contracting eczema vaccinatum (EV), a potentially fatal complication of smallpox vaccinations.

A critical host defense defect uncovered in patients with AD is their apparent relative lack of expression of antimicrobial peptides (AMPs), specifically cathelicidins, under inflammatory conditions. AMPs are important effectors and triggers in the innate immune system, and the lack of expression in AD patients could be a key component in their susceptibility to EV.

This study will examine whether or not administration of oral Vitamin D3 given over 21 days will change the AMP expression in the skin or saliva of AD subjects and healthy controls.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3LARLT608
Subjects: 90
Study PI, contact:
NameOrganizationSite
Donald Leung National Jewish Health National Jewish Health
Jon Hanifin Oregon Health & Science University Oregon Health & Science University
Richard Gallo University of California at San Diego University of California at San Diego
Publications:None
Resources:
ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00789880]
Assays:None
Clinical Assessments:
Any Adverse Event?
Any medications taken
Atopic Dermatitis Assessment
EASI Score
Family History
Fitzpatrick skin scale assessment
Medical History
Non-AD Assessment
Physical/Oral Exam
Rajka-Langeland Score
Skin exam
Skin lesion Involved and skin lesion duration
Smoking Status
Vital sign
SDY14: Antimicrobial Response to Oral Vitamin D3 in Patients with Psoriasis
Status: New
Description: The goal of the Atopic Dermatitis and Vaccinia Network (ADVN) is to research methods for preventing atopic dermatitis (AD) subjects from contracting eczema vaccinatum (EV), a potentially fatal complication of smallpox vaccinations.

A critical host defense defect uncovered in subjects with AD is their apparent relative lack of expression of antimicrobial peptides (AMPs), specifically cathelicidins, under inflammatory conditions. AMPs are important effectors and triggers in the innate immune system, and the lack of expression of these peptides in AD patients could be a key component in their susceptibility to EV.

The main Vitamin D3 study will examine whether or not the administration of oral Vitamin D3 over 21 days will change the AMP expression in the skin and saliva of AD subjects and healthy controls. Many new avenues of research are also being explored in this subject population and require initial exploratory data to be collected to assess their potential.

As an addition to the Antimicrobial Response to Oral Vitamin D protocol, this substudy protocol will provide further control information on psoriatic responses to oral vitamin D; information on bacterial colonization in AD, non-AD, and psoriatic subjects; and assess tape stripping as a noninvasive method for the measurement of cathelicidin skin expression.
Program/Contract:
ProgramContract
Atopic Dermatitis & Vaccinia Network (ADVN) Atopic Dermatitis and Vaccinia Network (ADVN) Clinical Studies Consort-26629c
DOI: 10.21430/M3U5ABTPCJ
Subjects: 62
Study PI, contact:
NameOrganizationSite
Richard Gallo University of California at San Diego University of California at San Diego
Publications:
A randomized controlled double-blind investigation of the effects of vitamin D dietary supplementation in subjects with atopic dermatitis.. J Eur Acad Dermatol Venereol. Jun 2014. doi: 10.1111/jdv.12176. Epub 2013 May 3. [Pubmed: 23638978]
Resources:
ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT00789880]
Assays:None
Clinical Assessments:
Any Adverse Event?
Any medications taken
Atopic Dermatitis Assessment
EASI Score
Family History
Fitzpatrick skin scale assessment
Medical History
Non-AD Assessment
Physical/Oral Exam
Psoriasis Area and Severity Index
Rajka-Langeland Score
Skin exam
Skin lesion Involved and skin lesion duration
Smoking Status
Vital sign
SDY16: Susceptibility and Resistance to Common Encapsulated Bacteria Infections
Status: New
Description: To study those patients who have history of at least one of 3 severe bacterial infections, S. pneumoniae, N. meningitides, and H. influenza. By asking what susceptibility genes that such patients have in common, we may find genes in pathways involved in resistance and susceptibility of a broader range of pathogens.

Variants that correlate with a relatively common trait like encapsulated bacterial susceptibility and sepsis will likely alter expression or splicing rather than be coding mutations in most cases. Therefore, our initial functional validation of the host genes that we find in GWAS will be to look for differences in amounts of mRNA in circulating white cells in the context of sepsis that lead to death and longer hospitalization compared to cases that have better outcomes.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Population Genetics Analysis Program: Immunity to Vaccines/Infections
DOI: 10.21430/M3FOZZ059R
Subjects: 142
Study PI, contact:
NameOrganizationSite
Jeffrey Gulcher deCODE
Publications:None
Resources:
Assays:
Assay TypeNumber of Exp. Samples
Sequencing 1
SNP microarray 6
Clinical Assessments:None
SDY17: Susceptibility to Influenza Infection and Complications
Status: New
Description: Many descendents of Spanish flu victims and survivors have given broad consent to deCODE's research and have been genotyped on the 370K chip. Using the chip data from the descendants, we have imputed genotypes of the Spanish flu victims and survivors of the same birth cohort to enable genome-wide association studies to identify markers associated with risk for severe outcome of H1N1 influenza.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Population Genetics Analysis Program: Immunity to Vaccines/Infections
DOI: 10.21430/M3H2I5WF3K
Subjects: 4
Study PI, contact:
NameOrganizationSite
Jeffrey Gulcher deCODE
Publications:None
Resources:
Assays:None
Clinical Assessments:None
SDY18: Immunity to Smallpox Vaccination
Status: New
Description: We propose to put together a program that combines one of the largest collections of recorded vaccine responses in the world with our extensive genealogy and genotyping capacity, thereby facilitating the mapping and isolation of key host response genes to smallpox virus vaccine.

Variants for a relatively common trait that correlates to smallpox vaccine response will likely alter expression or splicing rather than be coding mutations. Therefore, our initial functional validation of the host genes that we find in GWAS will be to look for differences in amounts of mRNA in the cultured peripheral blood mononuclear cells (PBMNs) from human volunteers with or without in vitro stimulation with vaccinia.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Population Genetics Analysis Program: Immunity to Vaccines/Infections
DOI: 10.21430/M39S5FJE1X
Subjects: 10
Study PI, contact:
NameOrganizationSite
Jeffrey Gulcher deCODE
Publications:None
Resources:
Assays:
Assay TypeNumber of Exp. Samples
DNA microarray 8
SNP microarray 4
Clinical Assessments:None
SDY19: Susceptibility and Resistance to Tuberculosis
Status: New
Description: In Iceland tuberculosis was relatively common around the Second World War and a few thousand cases have been documented by the central universal access healthcare system since the 1930s. Extensive surveillance has been performed on exposed members and we also have information on those who convert but did not develop an infection. The BCG vaccine has never been used in Iceland; therefore, Iceland has an ideal population because this allows for very accurate documentation of those who were exposed and converted by a positive Mantoux skin test but did not come down with an infection. Mapping genes involved in these responses could yield valuable information about host susceptibility or resistance factors that determine vulnerability to mycobacterium tuberculosis infections.

Therefore, our initial functional validation of the host genes that we find in GWAS will be to look for differences in amounts of mRNA and protein expressed in cultured peripheral blood mononuclear cells (PBMNs) from human volunteers with or without in vitro stimulation with M.tb. pathogen.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Population Genetics Analysis Program: Immunity to Vaccines/Infections
DOI: 10.21430/M30B3LE7S5
Subjects: 8
Study PI, contact:
NameOrganizationSite
Jeffrey Gulcher deCODE
Publications:None
Resources:
Assays:
Assay TypeNumber of Exp. Samples
SNP microarray 6
Clinical Assessments:None
SDY20: Assess the association between immune response genotype set and susceptibility to neuroinvasive disease.
Status: New
Description: We propose to identify polymorphic immune response genes associated with neurological complications to WNv infection. Our preliminary draft of 156 genes is based on three separate strategies.

First 100 immune related genes showing the highest levels of change (healthy volunteer peripheral blood was used as control) in gene expression profiles of peripheral blood RNA from 15 acutely ill WNv patients formed the bulk of the preliminary list. Twenty-five additional genes were based on the maximum change in expression of WNv infected vero cells. The remainder of the genes were based on studies reported in the literature identifying genes with an association with WNv infection and susceptibility. We will perform gene analysis of these preliminary candidates using single nucleotide polymorphisms (SNPs) to compare gene frequencies between individuals with meningoencephalitis and those with West Nile virus fever using a case-control study design.

A second draft of candidate genes will be derived from previously recognized immune genes and uncharacterized genes showing maximum levels of change between participants with meningoencephalitis and cases of West Nile fever as determined in gene expression profiles. This second draft will utilize specimens obtained in a on-going prospective cohort study of newly infected WNv patients. We anticipate that another two panels of approximately 150 genes each will be considered for additional analysis.

The results of these findings will be used to perform functional analysis of candidate genes.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Population Genetics Analysis Program on West Nile Virus
DOI: 10.21430/M3H2LBOI83
Subjects: 1674
Study PI, contact:
NameOrganizationSite
Mark Loeb Pathology & Molecular Medicine and Clinical Epidemiology and Biostatistics McMaster University
Publications:None
Resources:
Assays:None
Clinical Assessments:None
SDY22: Genotype Polymorphism effects on Typhoid Vaccine responses.
Status: New
Description: The objective is to understand role of polymorphisms in genes of innate and adaptive immunity in modulating the response to vaccines for typhoid gastrointestinal tract infections by:
  1. Collecting blood and saliva from 1000 vaccine study participants for each vaccine in Kolkata, India, at days 1, 3, and 28.
  2. Determining vaccine-specific titers using ELISA, vibriocidal, and multiplex bead antibody assays.
  3. Discover and validate SNP polymorphisms in this population and screen all participant's DNA for SNPs to 14 innate immunity genes and genome scans for adaptive immunity genes.
  4. Characterize protein/peptide expression using LC/MS, immunoassay, and flow cytometry for protein mediators of innate/adaptive immunity and 22 proteins involved in cell stimulation and signal transduction; and 2-D gel MS/MS on 100-200 proteins, protein isoforms and protein fragments to determine more generalized effects of immune activation, signal transduction and general response to vaccination.
  5. Determine haplotypes, perform association analyses between vaccine response (defined either categorically or quantitatively) and SNPs, haplotypes, or protein expression parameters, and perform association analyses between genomic and proteomic assessments.
  6. Conduct resequencing of genes with SNPs that are significantly associated to vaccine response.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Immune Response Polymorphisms: Typhoid/Cholera Vaccines
DOI: 10.21430/M36AEP1T4U
Subjects: 1003
Study PI, contact:
NameOrganizationSite
Diane Wagener Research Triangle Institute, NC "Research Triangle Institute, NC"
Publications:
Development of a bead immunoassay to measure Vi polysaccharide-specific serum IgG after vaccination with the Salmonella enterica serovar Typhi Vi polysaccharide.. Clin Vaccine Immunol. Mar 2010. doi: 10.1128/CVI.00354-09. Epub 2010 Jan 27. [Pubmed: 20107010]
Evaluation of vaccine-induced antibody responses: impact of new technologies.. Vaccine. Jun 2013. doi: 10.1016/j.vaccine.2013.03.065. Epub 2013 Apr 11. [Pubmed: 23583812]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
2D Gel 1
ELISA 1
Luminex xMAP 3
Mass Spectrometry 3
Clinical Assessments:None
SDY23: Genotype Polymorphism effects on Cholera Vaccine responses.
Status: New
Description: The objective is to understand role of polymorphisms in genes of innate and adaptive immunity in modulating the response to vaccines for cholera gastrointestinal tract infections by:
  1. Collecting blood and saliva from 1000 vaccine study participants for each vaccine in Kolkata, India, at days 1, 3, and 28.
  2. Determining vaccine-specific titers using ELISA, vibriocidal, and multiplex bead antibody assays.
  3. Discover and validate SNP polymorphisms in this population and screen all participant's DNA for SNPs to 14 innate immunity genes and genome scans for adaptive immunity genes.
  4. Characterize protein/peptide expression using LC/MS, immunoassay, and flow cytometry for protein mediators of innate/adaptive immunity and 22 proteins involved in cell stimulation and signal transduction; and 2-D gel MS/MS on 100-200 proteins, protein isoforms and protein fragments to determine more generalized effects of immune activation, signal transduction and general response to vaccination.
  5. Determine haplotypes, perform association analyses between vaccine response (defined either categorically or quantitatively) and SNPs, haplotypes, or protein expression parameters, and perform association analyses between genomic and proteomic assessments.
  6. Conduct resequencing of genes with SNPs that are significantly associated to vaccine response.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Immune Response Polymorphisms: Typhoid/Cholera Vaccines
DOI: 10.21430/M3J2PT6AOR
Subjects: 1000
Study PI, contact:
NameOrganizationSite
Diane Wagener Research Triangle Institute, NC "Research Triangle Institute, NC"
Publications:None
Resources:
Assays:
Assay TypeNumber of Exp. Samples
2D Gel 1
ELISA 2
Flow Cytometry 1
Luminex xMAP 3
Mass Spectrometry 2
Clinical Assessments:None
SDY24: Genetic Associations in subjects of anthrax trial [Anthrax Vaccine Adsorbed: Human Reactogenicity and Immunogenicity Trial to Address Change in Route of Administration and Dose Reduction (AVA000)]
Status: New
Description:

AVA000 is an ongoing 43-month prospective, randomized, double-blinded, placebo controlled comparison of AVA administered either SQ or IM in up to 8 doses (licensed regimen) or as few as 4 doses. From inception the trial has been on schedule in enrolling 1,560 healthy adults (as of 07/2003, 1480 subjects) at 5 clinical sites in the US, randomized into six study groups with 260 per group. Group 1 receives the licensed regimen (8 doses, SQ), and groups 2-5 receive 4-8 doses, IM. Group 6 receives placebo, either SQ or IM.

For immunogenicity analysis, blood samples are obtained from all subjects at enrollment, then prior to and 4 weeks after each injection (except at week 2). Levels of AbPA are measured in all subjects at all time points. A functional in vitro toxin (PA) neutralization assay is also performed on a subset of serum samples. For reactogenicity analysis, all adverse events, including local reactions at the injection sites, are actively monitored with both subject diaries and objective assessments by research study staff.

Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Population Genetics Analysis Program: Immunity to Vaccines/Infections
DOI: 10.21430/M3TT5SPDGV
Subjects: 1563
Study PI, contact:
NameOrganizationSite
Richard Kaslow University of Alabama at Birmingham "University of Alabama, Birmingham"
Publications:
Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial.. JAMA. Oct 2008. doi: 10.1001/jama.300.13.1532. [Pubmed: 18827210]
The role of HLA-DR-DQ haplotypes in variable antibody responses to anthrax vaccine adsorbed.. Genes Immun. Sep 2011. doi: 10.1038/gene.2011.15. Epub 2011 Mar 3. [Pubmed: 21368772]
Human leukocyte antigens and cellular immune responses to anthrax vaccine adsorbed.. Infect Immun. Jul 2013. doi: 10.1128/IAI.00269-13. Epub 2013 May 6. [Pubmed: 23649091]
Genomic copy number variants: evidence for association with antibody response to anthrax vaccine adsorbed.. PLoS One. May 2013. doi: 10.1371/journal.pone.0064813. Print 2013. [Pubmed: 23741398]
Resources:
Clinicaltrials.gov http://clinicaltrials.gov/ct2/show/NCT00119067]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 17980
HLA Typing 949
Clinical Assessments:None
SDY25: Genotyping and gene function in healthy volunteers
Status: New
Description:

The goal of this study is to create a pool of potential subjects genotyped in a manner identical to that used in the AVA000 trial population.

Subjects were screened for exclusion based on history of chronic infectious or immune diseases and to avoid sampling during current acute infection. Genotyping data are available for reference purposes. The subjects agreed to be available to be recalled for sampling of blood for ex vivo studies of differential immunologic function of genetic variants corresponding to those associated with variation in vaccine response.

Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Population Genetics Analysis Program: Immunity to Vaccines/Infections
DOI: 10.21430/M3L5GO913J
Subjects: 1423
Study PI, contact:
NameOrganizationSite
Richard Kaslow University of Alabama at Birmingham "University of Alabama, Birmingham"
Publications:
The role of HLA-DR-DQ haplotypes in variable antibody responses to anthrax vaccine adsorbed.. Genes Immun. Sep 2011. doi: 10.1038/gene.2011.15. Epub 2011 Mar 3. [Pubmed: 21368772]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
ELISA 2
Other 1
Clinical Assessments:None
SDY26: Identify polymorphisms associated with risk for the development of myopericarditis following smallpox vaccine
Status: New
Description: The overall goal of this contract is to identify genetic differences that increase the risk for a major adverse event associated with smallpox vaccination - myocarditis - and to determine the mechanism by which these genetic differences confer risk.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Genetic Risk for Smallpox Vaccine Related to Myocarditis
DOI: 10.21430/M389L5FQCN
Subjects: 410
Study PI, contact:
NameOrganizationSite
Christopher Wilson University of Washington University of Washington PGA
Publications:None
Resources:
Assays:
Assay TypeNumber of Exp. Samples
HLA Typing 312
Other 4
Clinical Assessments:None
SDY28: Humoral and Cell-Mediated Immune Responses to Vaccinia Virus Immunization
Status: New
Description: Our broad objective is to examine the role of candidate human immune response gene polymorphisms (and their receptors, expression and function) in inter-individual variability in vaccinia vaccine-induced humoral and cell-mediated immune responses among a cohort of 1,000 recently vaccinated subjects.

In Research Area 1, we propose to study associations between specific class I and II HLA alleles (HLA-A, -B, -C, -DRB, -DQA, -DQB, -DPA, -DPB), specific cytokine genes, polymorphisms of the above cytokine receptors, a genome-wide SNP analysis; and variations in immune response to smallpox vaccine.

In Research Area 2, we focus on identifying associations between expression and function of these same candidate genes likely to regulate immune response variations and humoral and cell-mediated immune responses following smallpox vaccination in selected human subjects. Both gene products (i.e., secreted proteins), cell surface expression, and measures of gene regulation/activation will be pursued. We focus on gene families involved in initiating, sustaining and regulating innate and adaptive immune responses, as well as those directly involved in directing specific antibody and cytotoxic T cell responses.
Program/Contract:
ProgramContract
Population Genetics Analysis Program (1) Population Genetics Analysis Program: Immunity to Vaccines/Infections
DOI: 10.21430/M3K3UZWK6S
Subjects: 1092
Study PI, contact:
NameOrganizationSite
Gregory Poland Mayo Vaccine Research Group "Mayo Clinic, Rochester MN"
Publications:
Response surface methodology to determine optimal cytokine responses in human peripheral blood mononuclear cells after smallpox vaccination.. J Immunol Methods. Feb 2009. doi: 10.1016/j.jim.2008.11.001. Epub 2008 Nov 25. [Pubmed: 19038260]
High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.. J Infect Dis. Nov 2012. doi: 10.1093/infdis/jis546. Epub 2012 Sep 4. [Pubmed: 22949304]
Transcriptomic profiles of high and low antibody responders to smallpox vaccine.. Genes Immun. Jul 2013. doi: 10.1038/gene.2013.14. [Pubmed: 23594957]
Race and sex-based differences in cytokine immune responses to smallpox vaccine in healthy individuals.. Hum Immunol. Oct 2013. doi: 10.1016/j.humimm.2013.06.031. Epub 2013 Jun 24. [Pubmed: 23806267]
The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine.. PLoS One. Aug 2016. doi: 10.1371/journal.pone.0158016. eCollection 2016. [Pubmed: 27513748]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
DNA microarray 426
ELISA 67862
ELISPOT 12756
Flow Cytometry 806
HLA Typing 1071
Clinical Assessments:None
SDY33: Impact of immunosuppressive regimens on protective immunity in renal transplant recipients
Status: New
Description: A prospective longitudinal study comparing renal transplant patients with controls to determine the biological mechanisms that underlie the immunosuppressed state associated with immunosuppressive regimens after transplantation.
Program/Contract:
ProgramContract
Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations Protective Immunity in Transplant Recipients
DOI: 10.21430/M3TJ6DJLEY
Subjects: 116
Study PI, contact:
NameOrganizationSite
Christian Larsen Emory Transplant Center "Emory Transplant Center, GA"
Publications:
Rapid cloning of high-affinity human monoclonal antibodies against influenza virus.. Nature. May 2008. doi: 10.1038/nature06890. Epub 2008 Apr 30. [Pubmed: 18449194]
Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen.. Nat Protoc. - 2009. doi: 10.1038/nprot.2009.3. [Pubmed: 19247287]
Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection.. J Exp Med. Jan 2011. doi: 10.1084/jem.20101352. Epub 2011 Jan 10. [Pubmed: 21220454]
Resources:
PMC http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039865/]
Assays:
Assay TypeNumber of Exp. Samples
DNA microarray 129
ELISPOT 12
Flow Cytometry 2223
HLA Typing 113
Clinical Assessments:None
SDY34: Comparison of immune response to influenza vaccine in transplant patients and healthy controls
Status: New
Description: This is a prospective longitudinal study to determine the effects of chronic immunosuppressive therapies on the magnitude and character of the adaptive immune response to influenza vaccination in healthy controls compared to renal transplant patients.
Program/Contract:
ProgramContract
Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations Protective Immunity in Transplant Recipients
DOI: 10.21430/M3KEDFBDQ7
Subjects: 97
Study PI, contact:
NameOrganizationSite
Christian Larsen Emory Transplant Center "Emory Transplant Center, GA"
Publications:
Rapid cloning of high-affinity human monoclonal antibodies against influenza virus.. Nature. May 2008. doi: 10.1038/nature06890. Epub 2008 Apr 30. [Pubmed: 18449194]
Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen.. Nat Protoc. - 2009. doi: 10.1038/nprot.2009.3. [Pubmed: 19247287]
Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection.. J Exp Med. Jan 2011. doi: 10.1084/jem.20101352. Epub 2011 Jan 10. [Pubmed: 21220454]
Resources:
PMC http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039865/]
Assays:
Assay TypeNumber of Exp. Samples
DNA microarray 21
Flow Cytometry 448
HLA Typing 42
Clinical Assessments:None
SDY35: Responses to and control of vaccinia in immunosuppressed Rhesus Macaques
Status: New
Description: A detailed mechanistic study of the immune response to vaccinia vaccine in immunosuppressed Rhesus macaques and development of a relevant preclinical model in which the efficacy and safety of vaccines in the setting of transplantation can be evaluated.
Program/Contract:
ProgramContract
Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations Protective Immunity in Transplant Recipients
DOI: 10.21430/M381YQIYXY
Subjects: 19
Study PI, contact:
NameOrganizationSite
Christian Larsen Emory Transplant Center "Emory Transplant Center, GA"
Publications:
Sirolimus enhances the magnitude and quality of viral-specific CD8+ T-cell responses to vaccinia virus vaccination in rhesus macaques.. Am J Transplant. Mar 2011. doi: 10.1111/j.1600-6143.2010.03407.x. [Pubmed: 21342450]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
DNA microarray 24
ELISA 31
Flow Cytometry 3433
Clinical Assessments:None
SDY36: Immune response of patients during pregnancy
Status: New
Description: To study whether the different trimesters in a unique hormone environment are associated with...

(a) Identifiable, discrete changes in maternal systemic immunity and/or

(b) recognizable alterations in susceptibility to select biodefense pathogens.

By challenging patient's cells with chimeric NDV viruses the study will investigate immune antagonists from category A-C pathogens and determine whether pregnancy changes in immune responses may lead to more profound pathogen specific immunodeficiency.

NK, T, plasmacytoid and myeloid dendritic cells will be evaluated without stimulation as well as evaluated in experiments after virus challenge. Cytokine and chemokine expression will also be assessed to determine whether cytokine expression patterns can be predicted in an individual and whether a specific pattern of cytokine expression is related to gestational age.
Program/Contract:
ProgramContract
Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations Immune Response to Virus Infection During Pregnancy
DOI: 10.21430/M3W4XGM811
Subjects: 58
Study PI, contact:
NameOrganizationSite
Thomas Moran School of Medicine Mount Sinai Hospital
Publications:
Characterizing the pregnancy immune phenotype: results of the viral immunity and pregnancy (VIP) study.. J Clin Immunol. Apr 2012. doi: 10.1007/s10875-011-9627-2. Epub 2011 Dec 24. [Pubmed: 22198680]
Immunogenicity of trivalent inactivated influenza vaccination received during pregnancy or postpartum.. Obstet Gynecol. Mar 2012. doi: 10.1097/AOG.0b013e318244ed20. [Pubmed: 22353963]
The influence of pregnancy on systemic immunity.. Immunol Res. Dec 2012. doi: 10.1007/s12026-012-8303-9. [Pubmed: 22447351]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
ELISA 5362
Flow Cytometry 259
Q-PCR 1146
Clinical Assessments:None
SDY37: Response of women during pregnancy to the inactivated influenza virus vaccine
Status: New
Description: Study volunteers will be recruited from the two obstetrical practices or the post-partum floor that are on-site at the Mount Sinai Medical Center, including the Obs/Gyn Diagnostic and Treatment Center (DTC) and Faculty Practice Associates (FPA). The DTC practice is the MSSM clinical teaching practice.

All patients will be required to give three blood samples, one at the time of the first study visit, the second 1-3 month(s) later (at the time of the second study visit), and the third at the end of flu season (end of March) in order to assess the immune response to routinely administered influenza vaccination(s). Relevant medical records will be reviewed to abstract detailed information about pregnancy complications and newborn outcomes.

In addition, when the study team is available, cord blood samples and placenta samples may be collected. These will be collected after specimens are processed as needed clinically and before remaining blood and tissues would otherwise be discarded.
Program/Contract:
ProgramContract
Immune Function and Biodefense in Children, Elderly, and Immunocompromised Populations Immune Response to Virus Infection During Pregnancy
DOI: 10.21430/M3BGAHTYYO
Subjects: 335
Study PI, contact:
NameOrganizationSite
Thomas Moran Department of Microbiology, Mount Sinai Health System Mount Sinai Hospital
Publications:
Immunogenicity of trivalent inactivated influenza vaccination received during pregnancy or postpartum.. Obstet Gynecol. Mar 2012. doi: 10.1097/AOG.0b013e318244ed20. [Pubmed: 22353963]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
ELISA 304
Hemagglutination Inhibition 4339
Clinical Assessments:None
SDY38: CD8+ T cell immunity to 2009 pandemic and seasonal H1N1 influenza viruses
Status: New
Description: Flow cytometry was used to measure the expression of IL2, IFN gamma and TNF alpha in CD8+ peripheral blood mononuclear cells isolated from 12 pH1N1 naive, healthy donors were stimulated in vitro with A/California/04/09 (pH1N1 strain, egg-grown), A/New Caledonia/20/09 (sH1N1, egg-grown), X31 (A/Puerto Rico H1N1 internal proteins, A/Hong Kong.
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) New York Influenza Center of Excellence
DOI: 10.21430/M3P9T1UFB9
Subjects: 12
Study PI, contact:
NameOrganizationSite
David Topham New York Influenza Center of Excellence New York Influenza Center of Excellence
Publications:
CD8+ T cell immunity to 2009 pandemic and seasonal H1N1 influenza viruses.. Vaccine. Mar 2011. doi: 10.1016/j.vaccine.2010.12.073. Epub 2011 Jan 4. [Pubmed: 21211588]
Resources:
Influenza Research Database http://www.fludb.org/brc/influenza_experiment_search.do?method=SubmitForm&experimentType=ImmportExperiment&decorator=influenza]
Assays:
Assay TypeNumber of Exp. Samples
Flow Cytometry 48
Clinical Assessments:None
SDY39: CD4+ T Cells Generated from Encounter with Seasonal Influenza Viruses and Vaccines Can Recognize Epitopes Derived from Pandemic H1N1 Virus
Status: New
Description: ELISPOT was used to enumerate the number of IFN gamma-secreting CD4+ peripheral blood mononuclear cells isolated from healthy naive donors following stimulation with APCs treated with peptide pools or whole virus
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) New York Influenza Center of Excellence
DOI: 10.21430/M3WC8VQ7OI
Subjects: 22
Study PI, contact:
NameOrganizationSite
Andrea Sant University of Rochester Medical Center University of Rochester Medical Center
Publications:
Cutting edge: CD4 T cells generated from encounter with seasonal influenza viruses and vaccines have broad protein specificity and can directly recognize naturally generated epitopes derived from the live pandemic H1N1 virus.. J Immunol. Nov 2010. doi: 10.4049/jimmunol.1001395. Epub 2010 Oct 1. [Pubmed: 20889549]
Resources:
Influenza Research Database http://www.fludb.org/brc/influenza_experiment_search.do?method=SubmitForm&experimentType=ImmportExperiment&decorator=influenza]
Immune Epitope Database (IEDB) http://www.iedb.org/reference/1021179]
Assays:
Assay TypeNumber of Exp. Samples
ELISPOT 163
Clinical Assessments:None
SDY42: Replication and pathogenesis associated with H5N1 H5N2 and H5N3 low-pathogenic avian influenza virus infection in chickens and ducks
Status: New
Description: A comparative cohort study examining replication and disease pathogenesis associated with low-pathogenic H5N1, H5N2, or H5N3 avian influenza virus (AIV) infection of chickens and ducks was performed.
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) Influenza Pathogenesis & Immunology Research Center (IPIRC)
DOI: 10.21430/M3YBOSJZIJ
Subjects: 8
Study PI, contact:
NameOrganizationSite
Egbert Mundt College of Veterinary Medicine, University of Georgia
Publications:
Replication and pathogenesis associated with H5N1, H5N2, and H5N3 low-pathogenic avian influenza virus infection in chickens and ducks.. Arch Virol. - 2009. doi: 10.1007/s00705-009-0437-2. Epub 2009 Jul 3. [Pubmed: 19575275]
Resources:
PubMed http://www.ncbi.nlm.nih.gov/pubmed/19575275]
Assays:
Assay TypeNumber of Exp. Samples
Hemagglutination Inhibition 88
Microscopy 96
Clinical Assessments:None
SDY44: Comparative Pathology in Ferrets Infected with H1N1 Influenza A Viruses Isolated from Different Hosts
Status: New
Description: Virus replication and pulmonary disease pathogenesis in ferrets following intranasal infection with a pandemic influenza virus strain (A/California/4/09 [CA09]), a human seasonal influenza H1N1 virus isolate (A/New Caledonia/20/99 [Ncal99]), a classical swine influenza H1N1 virus isolate (A/Swine/Iowa/15/30[Sw30]), or an avian H1N1 virus isolate (A/Mallard/MN/A108-2355/08 [Mal08]) were compared.
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) Influenza Pathogenesis & Immunology Research Center (IPIRC)
DOI: 10.21430/M30ZXXDZLP
Subjects: 8
Study PI, contact:
NameOrganizationSite
Ralph Tripp College of Veterinary Medicine, University of Georgia "College of Veterinary Medicine, University of Georgia"
Publications:
Comparative pathology in ferrets infected with H1N1 influenza A viruses isolated from different hosts.. J Virol. Aug 2011. doi: 10.1128/JVI.00512-11. Epub 2011 May 18. [Pubmed: 21593156]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
Hemagglutination Inhibition 8
Microscopy 140
Other 24
TCID50 34
Clinical Assessments:None
SDY51: Original Antigenic Sin Responses to Influenza Viruses
Status: New
Description: Determining the extent to which original antigenic sin is induced by variant influenza viruses by using two related strains of influenza
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) Influenza Pathogenesis & Immunology Research Center (IPIRC)
DOI: 10.21430/M3P8MVPEKB
Subjects: 18
Study PI, contact:
NameOrganizationSite
Joshy Jacob Emory Vaccine Center, Emory University Emory Vaccine Center, Emory University
Publications:
Original antigenic sin responses to influenza viruses.. J Immunol. Sep 2009. doi: 10.4049/jimmunol.0900398. Epub 2009 Jul 31. [Pubmed: 19648276]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
Hemagglutination Inhibition 67
Other 15
Virus Neutralization 85
Clinical Assessments:None
SDY91: Rituximab for the Treatment of Wegener's Granulomatosis and Microscopic Polyangiitis (RAVE ITN021AI)
Status: New
Description:

Current conventional therapies for ANCA-associated vasculitis (AAV) are associated with high incidences of treatment failure, disease relapse, substantial toxicity, and patient morbidity and mortality. Rituximab is a monoclonal antibody used to treat non-Hodgkin's lymphoma. This study will evaluate the efficacy of rituximab with glucocorticoids in inducing disease remission in patients with severe forms of AAV (WG and MPA).

The study consists of two phases: a 6-month remission induction phase, followed by a 12-month remission maintenance phase. All participants will receive at least 1 g of pulse intravenous methylprednisolone or a dose-equivalent of another glucocorticoid preparation. Depending on the participant's condition, he or she may receive up to 3 days of intravenous methylprednisolone for a total of 3 g of methylprednisolone (or a dose-equivalent). During the remission induction phase, all participants will receive oral prednisone daily (1 mg/kg/day, not to exceed 80 mg/day). Prednisone tapering will be completed by the Month 6 study visit.

Participants will then be randomly assigned to one of two arms. Arm 1 participants will receive rituximab (375 mg/m^2) infusions once weekly for 4 weeks and cyclophosphamide (CYC) placebo daily for 3 to 6 months. Arm 2 participants will receive rituximab placebo infusions once weekly for 4 weeks and CYC daily for 3 to 6 months. During the remission maintenance phase, participants in Arm 1 will discontinue CYC placebo and start oral azathioprine (AZA) placebo daily until Month 18. Participants in Arm 2 will discontinue CYC and start AZA daily until Month 18. Participants who fail treatment before Month 6 will be crossed over to the other treatment arm unless there are specific contraindications. Participants in either group who reach clinical remission before they complete 6 months of therapy may switch from CYC/placebo to AZA/placebo if directed by their physicians.All participants will be followed for at least 18 months. Initially, study visits are weekly, progressing to monthly and then quarterly visits as the study proceeds. Blood collection will occur at each study visit.

Program/Contract:
ProgramContract
ITN: Collaborative Network for Clinical Research on Immune Tolerance Network Rituximab for the Treatment of Wegener's Granulomatosis and Microscopic Polyangiitis (RAVE), Immune Tolerance Network
DOI: 10.21430/M3TK42R0QR
Subjects: 197
Study PI, contact:
NameOrganizationSite
Ulrich Specks Mayo Clinic Mayo Clinic
John H. Stone Johns Hopkins University Johns Hopkins University
Publications:
Rituximab versus cyclophosphamide for ANCA-associated vasculitis.. N Engl J Med. Jul 2010. doi: 10.1056/NEJMoa0909905. [Pubmed: 20647199]
Circulating markers of vascular injury and angiogenesis in antineutrophil cytoplasmic antibody-associated vasculitis.. Arthritis Rheum. Dec 2011. doi: 10.1002/art.30615. [Pubmed: 21953143]
Circulating angiopoietin-2 as a biomarker in ANCA-associated vasculitis.. PLoS One. - 2012. doi: 10.1371/journal.pone.0030197. Epub 2012 Jan 18. [Pubmed: 22279570]
Efficacy of remission-induction regimens for ANCA-associated vasculitis.. N Engl J Med. Aug 2013. doi: 10.1056/NEJMoa1213277. [Pubmed: 23902481]
Pro: Should all patients with anti-neutrophil cytoplasmic antibody-associated vasculitis be primarily treated with rituximab?. Nephrol Dial Transplant. Jul 2015. doi: 10.1093/ndt/gfv217. Epub 2015 May 21. [Pubmed: 25999375]
Reanalysis of the Rituximab in ANCA-Associated Vasculitis trial identifies granulocyte subsets as a novel early marker of successful treatment.. Arthritis Res Ther. Sep 2015. doi: 10.1186/s13075-015-0778-z. [Pubmed: 26387933]
Design of the Rituximab in ANCA-associated Vasculitis (RAVE) Trial.. The Open Arthritis Journal Nov 2011. doi: 10.2174/1876539401104010001 [Pubmed: TBD_A]
Resources:
ImmuneTolerance.org http://www.immunetolerance.org/]
ImmuneTolerance.org https://www.itntrialshare.org/]
Clinicaltrials.gov http://clinicaltrials.gov/ct2/show/NCT00104299]
The Open Arthritis Journal https://www.immunetolerance.org/sites/files/2011.11%20OpenArthritisJournal_Specks%20%28RAVE%20Design%29.pdf]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 1175
Flow Cytometry 1151
Clinical Assessments:
Assignment
Baseline Height (cm)
Baseline Weight (kg)
BVAS/WG
Diagnosis
Flares
Prednisone Taper
Remission
SF-36
Vasculitis Damage Index
SDY100: PPARG and microRNA-146 in mucosal immune responses to C. difficile
Status: New
Description: Clostridium difficile is typically a harmless anaerobic bacterium but recently it has re-emerged as a facultative pathogen that can cause nosocomial diarrhea, colitis and even death. Peroxisome proliferator-activated receptor (PPAR) gamma has been implicated in the prevention of inflammation in autoimmune and infectious diseases; however, its role in the immunoregulatory mechanisms modulating host responses to C. difficile remains largely unknown. To characterize the role of PPAR gamma in C. difficile-associated disease (CDAD), immunity and gut pathology, we used a mouse model of C. difficile infection in wild-type and T cell-specific PPAR gamma null mice. The loss of PPAR gamma in T cells increased disease activity and colonic inflammatory lesions following C. difficile infection. Colonic expression of IL-17 was upregulated and IL-10 downregulated in colons of T cell-specific PPAR gamma null mice. Also, both the loss of PPAR gamma in T cells and C. difficile infection favored Th17 responses in spleen and colonic lamina propria of mice with CDAD. MicroRNA (miRNA)-sequencing analysis and RT-PCR validation indicated that miR-146b was significantly overexpressed in colons of C. difficile-infected mice. We next developed a computational model that predicts the upregulation of miR-146b, downregulation of the PPAR gamma co-activator NCOA4, and PPAR gamma, leading to upregulation of IL-17. Treatment of C. difficile-infected mice with the PPAR gamma agonist pioglitazone ameliorated colitis and suppressed pro-inflammatory gene expression. In conclusion, our data indicates that miRNA-146b and PPAR gamma may be implicated in the regulation of Th17 responses and colitis in C. difficile-infected mice.
Program/Contract:
ProgramContract
Modeling Immunity for Biodefense II Virginia Bioinformatics Institute Modeling Immunity for Biodefense Contract
DOI: 10.21430/M3XUDZGCYI
Subjects: 98
Study PI, contact:
NameOrganizationSite
Josep Bassaganya-Riera NIMML VBI
Raquel Hontecillas NIMML VBI
Publications:
Modeling the role of peroxisome proliferator-activated receptor gamma and microRNA-146 in mucosal immune responses to Clostridium difficile.. PLoS One. - 2012. doi: 10.1371/journal.pone.0047525. Epub 2012 Oct 11. [Pubmed: 23071818]
The role of peroxisome proliferator-activated receptor gamma in immune responses to enteroaggregative Escherichia coli infection.. PLoS One. - 2013. doi: 10.1371/journal.pone.0057812. Epub 2013 Feb 28. [Pubmed: 23469071]
Resources:
MIEP http://modelingimmunity.vbi.vt.edu/]
Assays:
Assay TypeNumber of Exp. Samples
Flow Cytometry 64
Other 96
Q-PCR 70
Clinical Assessments:None
SDY131: Pediatric Kidney Transplant Without Calcineurin Inhibitors (CN01)
Status: New
Description:

This protocol tests whether immunosuppression by IL-2r antibody, sirolimus, MMF, and alternate-day steroids will provide comparable graft survival for living donor recipients, compared to current immunosuppression, but with reduced complications of calcineurin inhibitors.

Evaluations prior to transplantation include a complete history and physical examination, CBC, liver function tests, and antibodies for CMV, EBV, HIV, HbsAG, and HCV.All appropriate vaccinations are provided before transplantation. Transplant recipients receive immunosuppression therapy using antibody induction (daclizumab), corticosteroids, mycophenolate mofetil, and sirolimus. Serum sirolimus levels are measured so that doses can be adjusted to maintain certain blood levels of the drug. Bactrim and ganciclovir are given for infection prophylaxis. If the patient has consistent high levels of fasting cholesterol, treatment with lipitor may be given. A transplant biopsy is performed at the time of the transplant and at 3, 6, and 12 months post transplantation and at times when a rejection is suspected. A radionuclide GFR is done at the same time points, and at 1, 24, and 36 months. The protocol biopsies, blood, and urine samples will be analyzed by genomic methods to determine differences in gene expression post transplantation. In the event of a first acute rejection, patients are treated with Solu-Medrol for 3 consecutive days. A second rejection (at the discretion of the transplant center) or severe rejection (Banff Grade 3) is treated with antibody therapy and, after a second or severe rejection, the immunosuppressant regimen is changed. Patients are followed for 36 months with routine physical examinations and laboratory assessments

Program/Contract:
ProgramContract
Cooperative Clinical Trials in Pediatric Transplantation (CCTPT) Data Coordinating Center for Cooperative Clinical Trials in Pediatric Transplantation
DOI: 10.21430/M38TWQ85KW
Subjects: 34
Study PI, contact:
NameOrganizationSite
William Harmon Boston Children's Hospital Boston Children's Hospital
Publications:
Short sirolimus half-life in pediatric renal transplant recipients on a calcineurin inhibitor-free protocol.. Pediatr Transplant. Apr 2004. doi: - [Pubmed: 15049798]
Measuring T cell alloreactivity to predict kidney transplant outcomes: are we there yet?. J Am Soc Nephrol. Feb 2006. doi: b 2005 Dec 28. [Pubmed: 16382014]
Safety and efficacy of a calcineurin inhibitor avoidance regimen in pediatric renal transplantation.. J Am Soc Nephrol. Jun 2006. doi: b 2006 May 10. [Pubmed: 16687625]
Subsets of human CD4(+) regulatory T cells express the peripheral homing receptor CXCR3.. Eur J Immunol. Aug 2011. doi: 10.1002/eji.201041095. Epub 2011 Jun 24. [Pubmed: 21538345]
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/record/NCT00023231]
Assays:
Assay TypeNumber of Exp. Samples
Q-PCR 12189
Clinical Assessments:
Graft_Outcome
REJECTION
SDY132: Tacrolimus with Steroids and Standard Daclizumab Versus Steroid-Free Tacrolimus with Extended Daclizumab in Pediatric Renal Transplantation (SNS01)
Status: New
Description:

Corticosteroids have been a cornerstone of immunosuppressive therapy for kidney transplantation for over 40 years. However, poor growth and bone loss caused by the use of corticosteroids are devastating to pediatric kidney recipients. The negative physical implications of corticosteroid use also greatly impacts patients' compliance to their prescribed corticosteroid-containing regimens. The development of a corticosteroid-free regimen for post-transplant pediatric patients is sorely needed. This study will evaluate the safety and efficacy of a corticosteroid-free treatment regimen in children and adolescents who have received kidney transplants, compared to a standard of care regimen including corticosteroids. Participants in this study will be pediatric patients with end-stage kidney disease who will undergo kidney transplantation at the start of the study.

Patients will participate in this study for 3 years. Participants will be randomly assigned to one of two groups. Group 1 patients will receive daclizumab, tacrolimus, mycophenolate mofetil (MMF), and prednisone. Group 1 patients will receive daclizumab prior to transplantation and at Weeks 2, 4, 6, and 8 after transplantation. Group 1 patients will receive prednisone at the time of transplantation and will undergo gradual prednisone tapering post-transplant. Group 2 patients will receive daclizumab, tacrolimus, MMF, but no prednisone. Group 2 patients will receive daclizumab prior to transplantation, at Weeks 2, 4, 6, 8, and 11, and at Months 4, 5 and 6 after transplantation. To prevent opportunistic infections, all patients will receive prophylactic medications beginning after transplantation.

There will be 23 study visits during the 3-year study. A physical exam, medication history, adverse events reporting, blood pressure readings, growth assessment, and blood collection will occur at most visits. At the time of transplantation, patients will have a kidney biopsy. Patients will also undergo cataract screening within 4 months of transplantation.

Program/Contract:
ProgramContract
Cooperative Clinical Trials in Pediatric Transplantation (CCTPT) Data Coordinating Center for Cooperative Clinical Trials in Pediatric Transplantation
DOI: 10.21430/M3ZOBVGDW6
Subjects: 130
Study PI, contact:
NameOrganizationSite
Oscar Salvatierra Stanford University Lucile Salter Packard Children?s Hospital
Publications:
Subclinical inflammation and chronic renal allograft injury in a randomized trial on steroid avoidance in pediatric kidney transplantation.. Am J Transplant. Oct 2012. doi: 10.1111/j.1600-6143.2012.04144.x. Epub 2012 Jun 13. [Pubmed: 22694733]
Complete steroid avoidance is effective and safe in children with renal transplants: a multicenter randomized trial with three-year follow-up.. Am J Transplant. Oct 2012. doi: 10.1111/j.1600-6143.2012.04145.x. Epub 2012 Jun 13. [Pubmed: 22694755]
A peripheral blood diagnostic test for acute rejection in renal transplantation.. Am J Transplant. Oct 2012. doi: 10.1111/j.1600-6143.2012.04253.x. [Pubmed: 23009139]
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT00141037]
Assays:
Assay TypeNumber of Exp. Samples
Q-PCR 3850
Clinical Assessments:None
SDY133: Steroid Withdrawal in Pediatric Kidney Transplant Recipients (SW01)
Status: New
Description:

Children receiving kidney (renal) transplantation face distressing issues in post-transplantation including but not limited to growth retardation directly attributable to corticosteroids (steroids). It is hypothesized that robust immunosuppression with sirolimus and calcineurin inhibitors (cyclosporine or tacrolimus) in conjunction with induction therapy should enable successful steroid withdrawal. A steroid-free environment could lessen side effects by enabling a child to achieve catch-up growth, reducing the need for anti-hypertensive therapy, and reducing the risk of cardiovascular disease. This trial tests the objective of providing a steroid-free state without incurring the risk of increased incidence of acute transplant rejections.

Patients are enrolled prior to kidney transplantation and receive standard evaluations. Patients receive induction therapy with basiliximab preoperatively and on Day 4 after surgery. Immunosuppressive therapy begins with sirolimus and either cyclosporine or tacrolimus on Day 1 following surgery, and with corticosteroids the day of surgery. Infection prophylaxis with Bactrim is begun on Day 1 after surgery and center-specific anti-cytomegalovirus (CMV) therapy is given for all recipients of a CMV positive kidney. At 6 months post-transplantation, all patients who have not had an episode of acute rejection undergo a renal graft biopsy. Patients who are confirmed to be free of subclinical rejection are randomized to either undergo complete steroid withdrawal or continue maintenance on daily steroids. Patients receive either steroids or placebo, while continuing other immunosuppressive medications. Patients are segregated into weight groups for steroid withdrawal that occurs over months 7 to 13. Any acute rejection event during withdrawal is confirmed by renal biopsy and managed with methylprednisolone treatment. Patients are followed for 3 years post-transplantation for analysis of growth rate, blood pressure, lipid profile and renal function as measured by serum creatinine and calculated creatinine clearances. Post-transplantation clinic visits are weekly for the first 2 months, every 2 weeks until 13 months, weekly during Month 13, every 2 weeks through Month 18, and monthly until the study ends.

Patients who exhibit evidence of acute or subclinical rejection do not continue the steroid withdrawal trial and care is managed by their pediatric renal transplant center physicians.

Program/Contract:
ProgramContract
Cooperative Clinical Trials in Pediatric Transplantation (CCTPT) Data Coordinating Center for Cooperative Clinical Trials in Pediatric Transplantation
DOI: 10.21430/M3HRUXROFP
Subjects: 272
Study PI, contact:
NameOrganizationSite
William Harmon Boston Children's Hospital Boston Children's Hospital
Publications:
Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids.. Am J Transplant. May 2008. doi: 10.1111/j.1600-6143.2008.02167.x. [Pubmed: 18416737]
A randomized double-blind, placebo controlled trial of steroid withdrawal after pediatric renal transplantation.. Am J Transplant. Jan 2010. doi: 10.1111/j.1600-6143.2009.02767.x. Epub 2009 Jul 28. [Pubmed: 19663893]
Steroids in pediatric kidney transplantation: a balancing act in progress.. Am J Transplant. Jan 2010. doi: 10.1111/j.1600-6143.2009.02923.x. Epub 2009 Dec 17. [Pubmed: 19958331]
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/record/NCT00023244]
Assays:None
Clinical Assessments:None
SDY134: Safety in Immunomodulatory Functions of Campath-1H (PC01)
Status: New
Description: Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). Improvements in surgical techniques, donor selection, and immunosuppression practices, as well as the enhanced experience of specialized pediatric transplant teams, have all led to marked improvements in patient and kidney graft survival in infants and young children ages 1 to 10. However, young children now have more infections following transplant previously. Also, improved graft survival is not observed in pediatric renal transplant recipients 11 to 17 years of age. Some studies do indicate that the poor long term outcome of patient and kidney survival observed in this age group may be caused by noncompliance with immunosuppressive medications. Therefore, protocols that minimize the use of immunosuppressive medications while retaining kidney function are necessary for improving graft and patient survival in children. This study will evaluate the safety of a regimen containing alemtuzumab after kidney transplantation, followed by steroid avoidance and calcineurin inhibitor withdrawal in pediatric renal transplant recipients 1 to 20 years of age.
Program/Contract:
ProgramContract
Cooperative Clinical Trials in Pediatric Transplantation (CCTPT) Data Coordinating Center for Cooperative Clinical Trials in Pediatric Transplantation
DOI: 10.21430/M3TUS7C3AN
Subjects: 35
Study PI, contact:
NameOrganizationSite
William Harmon Boston Children's Hospital Boston Children's Hospital
Publications:
Immune profile of pediatric renal transplant recipients following alemtuzumab induction.. J Am Soc Nephrol. Jan 2012. doi: 10.1681/ASN.2011040360. Epub 2011 Nov 3. [Pubmed: 22052056]
Resources:
clinicaltrials.gov http://clinicaltrials.gov/ct2/show/NCT00240994]
Assays:None
Clinical Assessments:None
Back to top