DR4 DataRelease

SDY95: Host Differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization
Status: New
Description: The antibody response to influenza infection is largely dependent on CD4 T cell help for B cells. Cognate signals and secreted factors provided by CD4 T cells drive B cell activation and regulate antibody isotype switching for optimal antiviral activity. Recently, we analyzed HLA-DR1 transgenic (DR1) mice and C57BL/10 (B10) mice after infection with influenza virus A/New Caledonia/20/99 (NC) and defined epitopes recognized by virus-specific CD4 T cells. Using this information in the current study, we demonstrate that the pattern of secretion of IL-2, IFN-g, and IL-4 by CD4 T cells activated by NC infection is largely independent of epitope specificity and the magnitude of the epitope-specific response. Interestingly, however, the characteristics of the virus-specific CD4 T cell and the B cell response to NC infection differed in DR1 and B10 mice. The response in B10 mice featured predominantly IFN-g-secreting CD4 T cells and strong IgG2b/IgG2c production. In contrast, in DR1 mice most CD4 T cells secreted IL-2 and IgG production was IgG1-biased. Infection of DR1 mice with influenza PR8 generated a response that was comparable to that in B10 mice, with predominantly IFN-g-secreting CD4 T cells and greater numbers of IgG2c than IgG1 antibody-secreting cells. The response to intramuscular vaccination with inactivated NC was similar in DR1 and B10 mice; the majority of CD4 T cells secreted IL-2 and most IgG antibody-secreting cells produced IgG2b or IgG2c. Our findings identify inherent host influences on characteristics of the virus-specific CD4 T cell and B cell responses that are restricted to the lung environment. Furthermore, we show that these host influences are substantially modulated by the type of infecting virus via the early induction of innate factors. Our findings emphasize the importance of immunization strategy for demonstrating inherent host differences in CD4 T cell and B cell responses.
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) New York Influenza Center of Excellence
DOI: 10.21430/M3HHUFK741
Subjects: 499
Study PI, contact:
NameOrganizationSite
Mark Sangster University of Rochester Medical Center ROC034
Publications:
Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization.. PLoS One. - 2012. doi: 10.1371/journal.pone.0034377. Epub 2012 Mar 23. [Pubmed: 22457834]
Resources:
Immune Epitope Database (IEDB) http://www.iedb.org/reference/1022961]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 422
ELISPOT 2556
Luminex xMAP 808
TCID50 126
Clinical Assessments:None
SDY99: Primary seasonal influenza virus infection elicits CD4 T cells specific for genetically conserved epitopes that can be mobilized for cross protective immunity to pandemic H1N1 influenza
Status: New
Description: In this study, a mouse model of primary and secondary influenza infection is developed by using a widely circulating seasonal H1N1 virus and the pandemic strain of H1N1 that emerged in Mexico in 2009, and several key issues are evaluated. The specificity of CD4 T cell reactivity toward epitopes conserved among H1N1 viruses or unique to the seasonal or pandemic strain was assessed by ELISpot assays. It was observed that a secondary challenge with the pandemic virus was associated with rapid expansion of memory CD4 T cells specific for shared determinants, decreased viral titers and accelerated neutralizing anti-influenza antibody responses to the serologically distant novel pandemic strain.
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) New York Influenza Center of Excellence
DOI: 10.21430/M3P4JJNFS2
Subjects: 266
Study PI, contact:
NameOrganizationSite
Andrea Sant University of Rochester Medical Center ROC034
Publications:
Infection with seasonal influenza virus elicits CD4 T cells specific for genetically conserved epitopes that can be rapidly mobilized for protective immunity to pandemic H1N1 influenza virus.. J Virol. Dec 2011. doi: 10.1128/JVI.05728-11. Epub 2011 Oct 5. [Pubmed: 21976658]
Resources:
Immune Epitope Database (IEDB) http://www.iedb.org/reference/1022612]
Assays:
Assay TypeNumber of Exp. Samples
ELISPOT 691
Other 331
TCID50 8
Virus Neutralization 51
Clinical Assessments:None
SDY139: The peptide specificity of the endogenous T follicular helper cell repertoire generated after protein immunization
Status: New
Description: T follicular helper (Tfh) cells potentiate high-affinity, class-switched antibody responses, the predominant correlate of protection from vaccines. Despite intense interest in understanding both the generation and effector functions of this lineage, little is known about the epitope specificity of Tfh cells generated during polyclonal responses. To date, studies of peptide-specific Tfh cells have relied on either the transfer of TcR transgenic cells or use of peptide:MHC class II tetramers and antibodies to stain TcR and follow limited peptide specificities. In order to comprehensively evaluate polyclonal responses generated from the natural endogenous TcR repertoire, we developed a sorting strategy to separate Tfh cells from non-Tfh cells and found that their epitope-specific responses could be tracked with cytokine-specific ELISPOT assays. The immunodominance hierarchies of Tfh and non-Tfh cells generated in response to immunization with several unrelated protein antigens were remarkably similar. Additionally, increasing the kinetic stability of peptide-MHC class II complexes enhanced the priming of both Tfh and conventional CD4 T cells. These findings may provide us with a strategy to rationally and selectively modulate epitope-specific Tfh responses. By understanding the parameters that control epitope-specific priming, vaccines may be tailored to enhance or focus Tfh responses to facilitate optimal B cell responses.
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) New York Influenza Center of Excellence
DOI: 10.21430/M3OM5T92K5
Subjects: 62
Study PI, contact:
NameOrganizationSite
Andrea Sant University of Rochester Medical Center ROC034
Publications:
The peptide specificity of the endogenous T follicular helper cell repertoire generated after protein immunization.. PLoS One. - 2012. doi: 10.1371/journal.pone.0046952. Epub 2012 Oct 15. [Pubmed: 23077537]
Resources:
Immune Epitope Database (IEDB) http://www.iedb.org/reference/1025214]
Assays:
Assay TypeNumber of Exp. Samples
ELISPOT 466
Flow Cytometry 100
Q-PCR 456
Clinical Assessments:None
SDY147: Analyses of the specificity of CD4 T Cells during the primary immune response to influenza virus reveals dramatic MHC-linked asymmetries in reactivity to individual viral proteins
Status: New
Description: Influenza is a contagious, acute respiratory disease that is a major cause of morbidity and mortality throughout the world. CD4 T cells play an important role in the immune response to this pathogen through the secretion of antiviral cytokines, and by providing help to CD8 T cells and B cells to promote the development of immunological memory and neutralizing antibody responses. Despite these well-defined roles in the anti-influenza response, our understanding of CD4 T-cell diversity and specificity remains limited. In the study reported here, overlapping peptides representing 5 different influenza viral proteins were used in EliSpot assays to enumerate and identify the specificity of anti-influenza CD4 T cells directly ex vivo following infection of mice with influenza virus, using two strains that express unrelated MHC class II molecules. These experiments evaluated whether the reactivity of CD4 T cells generally tracked with particular influenza proteins, or whether MHC preferences were the predominant factor dictating anti-CD4 T-cell specificity in the primary immune response. We made the unexpected discovery that the distribution of CD4 T-cell specificities for different influenza proteins varied significantly depending on the single class II molecule expressed in vivo. In SJL mice, the majority of epitopes were specific for the HA protein, while the NP protein dominated the response in C57BL/10 mice. Given the diversity of human MHC class II molecules, these findings have important implications for the ability to rationally design a vaccine that will generate a specific CD4 T-cell immune response that is effective across diverse human populations.
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) New York Influenza Center of Excellence
DOI: 10.21430/M38LME8QIB
Subjects: 80
Study PI, contact:
NameOrganizationSite
Andrea Sant University of Rochester Medical Center ROC034
Publications:
Analyses of the specificity of CD4 T cells during the primary immune response to influenza virus reveals dramatic MHC-linked asymmetries in reactivity to individual viral proteins.. Viral Immunol. Apr 2010. doi: 10.1089/vim.2009.0099. [Pubmed: 20373997]
Resources:
Immune Epitope Database (IEDB) http://www.iedb.org/reference/1019786]
Assays:
Assay TypeNumber of Exp. Samples
ELISPOT 1715
Clinical Assessments:None
SDY207: Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes
Status: New
Description: High dimensional analysis of CD8+ T cell phenotype and function
Program/Contract:
ProgramContract
Human Immunology Project Consortium 1 (HIPC1) Vaccination and infection: indicators of immunological health and responsiveness
DOI: 10.21430/M33C1GNCXF
Subjects: 6
Study PI, contact:
NameOrganizationSite
Mark Davis Stanford University Stanford University School of Medicine
Publications:
Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes.. Immunity. Jan 2012. doi: 10.1016/j.immuni.2012.01.002. [Pubmed: 22265676]
Resources:
None None]
Assays:
Assay TypeNumber of Exp. Samples
CyTOF 34
Clinical Assessments:None
SDY210: Asthma Control Evaluation (ACE): A Biomarker-Based Approach to Improving Asthma Control and Mechanistic Studies
Status: New
Description: Over the past two decades, the prevalence of asthma has dramatically increased in many parts of the world. The current National Asthma Education and Prevention Program (NAEPP) identifies inhaled corticosteroids (ICS) as the preferred long-term control therapy for all forms of persistent asthma. However, there is still a significant proportion of patients with persistent asthma who are not receiving ICS therapy or do not follow their treatment plan. Individualized asthma treatment plans are needed. The use of biomarkers, in addition to NAEPP guidelines, may help enhance the level of asthma assessment, guide medication regimens, and improve overall asthma control. This study will determine whether NAEPP-recommended treatment, combined with eNO measurement, is more effective in reducing asthma symptoms than NAEPP-recommended treatment alone. ICAC-01 will last 46 weeks and will comprise 8 study visits. ICAC-01 also includes a mechanistic sub-study (ICAC-02). Its primary objective is to determine whether highly sensitized, compared to weakly sensitized asthmatic subjects have more severe asthma, as defined by the levels at randomization to the completion of ICAC-01. To address the primary objective of ICAC-02, the study will include all the participants enrolled in ICAC-01 with dust mite-, cockroach- and/or alternaria-specific IgE levels within certain parameters.
Program/Contract:
ProgramContract
Inner City Asthma Consortium (ICAC) Inner City Asthma Consortium (ICAC)
DOI: 10.21430/M3I0JL7KUZ
Subjects: 546
Study PI, contact:
NameOrganizationSite
William Busse University of Wisconsin, Madison University of Wisconsin, Madison
Publications:
Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial.. Lancet. Sep 2008. doi: 10.1016/S0140-6736(08)61448-8. [Pubmed: 18805335]
Asthma severity, not asthma control, is worse in atopic compared with nonatopic adolescents with asthma.. Ann Allergy Asthma Immunol. Jan 2016. doi: 10.1016/j.anai.2015.10.015. Epub 2015 Nov 7. [Pubmed: 26560898]
Resources:
Clinicaltrials.gov http://www.clinicaltrials.gov/ct/show/NCT00114413]
Assays:None
Clinical Assessments:None
SDY211: Inner-City Anti-IgE Therapy for Asthma
Status: New
Description: This study is testing a medication called omalizumab for the treatment of asthma. Immunoglobulin E (IgE) is produced when one is exposed to allergens and it can cause inflammation in the lungs. Omalizumab can reduce inflammation and asthma attacks by blocking IgE. Unlike other medications for asthma, omalizumab is not an inhaler medication or pill. Instead, omalizumab is dissolved in a liquid and given by injection. Studies indicate that people living in the inner-city areas are more likely to be exposed to indoor allergens that are difficult to avoid than people living in other areas. The purpose of this study is to find out if adding omalizumab to standard asthma treatment results in a safer, more effective, and longer lasting asthma treatment strategy than standard treatment alone. This study will recruit inner-city children and adolescents with moderate to severe allergic asthma. This study will last about 1.5 to 2 years. Participants will be randomly assigned to receive either omalizumab or placebo injections once every 2 or 4 weeks. The injection schedule will be determined based on the participant's weight and total IgE. Both groups will receive standardized specialist care and basic asthma education including environmental control measures. Participants must have some form of health care insurance to cover the costs of asthma controller medications prescribed during the study. Participants will complete a series of questionnaires about topics including perceived stress, home environment, physical activity, diet and nutrition, smoking habits, and quality of life. At study entry and monthly throughout the study, participants will complete questionnaires about their asthma symptoms and medical resource utilization. Some visits will include a physical examination, vital signs measurement, lung function tests, asthma medication evaluation, and an asthma action plan. Blood collection is required up to eight times during the study for safety labs.
Program/Contract:
ProgramContract
Inner City Asthma Consortium (ICAC) Inner City Asthma Consortium (ICAC)
DOI: 10.21430/M3V7CAZ3NP
Subjects: 419
Study PI, contact:
NameOrganizationSite
William Busse University of Wisconsin, Madison University of Wisconsin, Madison
Publications:
Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children.. N Engl J Med. Mar 2011. doi: 10.1056/NEJMoa1009705. [Pubmed: 21410369]
Resources:
Clinicaltrials.gov http://www.clinicaltrials.gov/ct/show/NCT00377572]
Assays:None
Clinical Assessments:None
SDY217: Orchestration of CD4 T cell epitope preferences after multi-peptide immunization
Status: New
Description: A detailed understanding of the molecular and cellular mechanisms that underlie epitope preferences in T cell priming is important for vaccines designed to elicit a broad T cell response. Protein vaccinations generally elicit CD4 T cell responses that are skewed toward a small fraction of epitopes, a phenomenon known as immunodominance. This characteristic of T cell responses, that limits the diversity of CD4 T cell recognition, is generally attributed to intracellular antigen processing. However, we recently discovered that immunodominance hierarchies persist even after vaccination with synthetic peptides. In this study, we probed the regulatory mechanisms that cause diminished CD4 T cell responses to subdominant peptides after such multi-peptide immunization in mice. We have found that the delivery of subdominant and dominant epitopes on separate dendritic cells rescues expansion of less favored CD4 T cells. Furthermore, through the use of genetic models and inhibitors, we have found that selective losses in CD4 T cell responses are mediated by an IFN-gamma-induced pathway, involving indoleamine 2,3-dioxygenase (IDO), and that regulatory T cell (Treg) activities may also regulate preferences in CD4 T cell specificity. We propose that after multi-peptide immunization, the expansion and differentiation of dominant T cells initiate complex regulatory events that determine the final peptide specificity of the elicited CD4 T cell response.
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) New York Influenza Center of Excellence
DOI: 10.21430/M35YNXHF8K
Subjects: 283
Study PI, contact:
NameOrganizationSite
Andrea Sant University of Rochester Medical Center ROC034
Publications:
Orchestration of CD4 T cell epitope preferences after multipeptide immunization.. J Immunol. Jul 2013. doi: 10.4049/jimmunol.1300312. Epub 2013 Jun 14. [Pubmed: 23772029]
Resources:
Immune Epitope Database (IEDB) http://www.iedb.org/reference/1026471]
Assays:
Assay TypeNumber of Exp. Samples
ELISPOT 494
Flow Cytometry 64
Clinical Assessments:None
SDY223: A Biomarker-based Pilot Study of Cockroach Sublingual Immunotherapy in Cockroach Sensitive Adults With Asthma and/or Perennial Allergic Rhinitis
Status: New
Description: Over the last two decades, the prevalence of asthma has dramatically increased in many parts of the world. Currently, there are no effective ways to prevent the development of nasal allergies and asthma, and there are no cures for these diseases. Sublingual immunotherapy (SLIT) may help reduce symptoms of allergy and asthma. The purpose of this study is to evaluate the safety and efficacy of a cockroach extract given sublingually to adults with perennial (year-round) nasal allergies, asthma, or both. At study entry, participants will receive a dose of placebo and then up to five incremental doses of cockroach extract or placebo at 15-minute intervals while observed by the clinical research staff. Doses will continue to be given until a sign or symptom occurs that indicates the participant is having difficulty tolerating the drug, or until the maximum study dose is reached. For the next 6 months, participants will take the maximum study dose of cockroach extract or placebo daily at home. This study will consist of 8 study visits. Skin tests, breathing tests, and blood collection will occur at study screening and other visits during the study. At study entry, participants will be taught to use an EpiPen in the event of a severe allergic reaction at any time during the study. A physical and oral exam, breathing test, and blood collection will occur at study entry and all follow-up visits.
Program/Contract:
ProgramContract
Inner City Asthma Consortium (ICAC) Inner City Asthma Consortium (ICAC)
DOI: 10.21430/M34X4ULP41
Subjects: 54
Study PI, contact:
NameOrganizationSite
Robert Wood Johns Hopkins University School of Medicine Johns Hopkins University School of Medicine
Publications:None
Resources:
ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT00829985]
Assays:None
Clinical Assessments:None
SDY167: VRC304 - A Phase I Study of the Safety and Immunogenicity of a Recombinant DNA Plasmid Vaccine (VRC-AVIDNA036-00-VP) Encoding for the Influenza Virus H5 Hemagglutinin Protein in Healthy Adults
Status: Updated
Description: The primary objective was to evaluate the safety and tolerability of an investigational vaccine VRC-AVIDNA036-00-VP in humans at doses 1 mg and 4 mg administered intramuscularly using a needle-free injection system. The secondary objectives included evaluation of whether VRC-AVIDNA036-00-VP (at doses 1 mg and 4 mg) induced antibodies as assessed by an HAI assay at Day 0 and Week 12. Exploratory analyses included evaluation of the immunogenicity of VRC-AVIDNA036-00-VP at doses 1 mg and 4 mg using intracellular cytokine staining, ELISpot, neutralizing antibody assay, HAI assay to H1 or H3HA or other immunological assays at time intervals between Day 0 and Week 42.
Program/Contract:
ProgramContract
NIAID Vaccine Research Center (VRC) NIAID Vaccine Research Center (VRC)
DOI: 10.21430/M3SGHW16WZ
Subjects: 45
Study PI, contact:
NameOrganizationSite
Julie Ledgerwood Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID)
Publications:
Influenza virus h5 DNA vaccination is immunogenic by intramuscular and intradermal routes in humans.. Clin Vaccine Immunol. Nov 2012. doi: 10.1128/CVI.05663-11. Epub 2012 Sep 5. [Pubmed: 22956656]
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT00408109]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 430
ELISPOT 300
Flow Cytometry 874
Hemagglutination Inhibition 44
Virus Neutralization 88
Clinical Assessments:None
SDY208: Serological Memory and Long-term Protection to Novel H1N1 Influenza Virus After Skin Vaccination
Status: Updated
Description: Investigating the long-lived immunity and improved protection after skin vaccination
Program/Contract:
ProgramContract
NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) Influenza Pathogenesis & Immunology Research Center (IPIRC)
DOI: 10.21430/M3VGBJC7TC
Subjects: 7
Study PI, contact:
NameOrganizationSite
Richard Compans School of Medicine, Emory University Emory University
Publications:
Serological memory and long-term protection to novel H1N1 influenza virus after skin vaccination.. J Infect Dis. Aug 2011. doi: 10.1093/infdis/jir094. Epub 2011 Jun 17. [Pubmed: 21685355]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
ELISA 61
ELISPOT 9
Hemagglutination Inhibition 17
Microscopy 4
Clinical Assessments:None
SDY218: Oral Immunotherapy for Childhood Egg Allergy
Status: Updated
Description:

In the United States, as many as 6% to 8% of children are affected by food allergy. In young children, allergic reactions to egg can range from mild rash to systemic anaphylaxis. The usual standard of care for allergy is complete avoidance of this food allergen and treatment of accidental systemic reactions by access to self-injected epinephrine. However, accidental exposure to allergens in processed foods may be difficult to avoid. Currently, several therapeutic strategies are being investigated to prevent and treat food allergies. Since standard injection (under the skin) immunotherapy for food allergy is associated with a high rate of allergic reactions, a few studies have recently tried oral immunotherapy (OIT) in food allergy. The purpose of this study is to determine the safety and efficacy of the administration of OIT. The intent is to develop desensitization and eventually tolerance to egg allergen. This study will evaluate tolerance to egg white solid that may be gained by gradually increasing the amounts of egg white solid given to a child over a long period of time. This study will last up to 48 months. The participants will be randomly assigned to receive oral immunotherapy treatment with egg white solid or placebo. This study will include dose escalation and maintenance followed by oral food challenge (OFC).

For participants receiving egg OIT, visit 1 consists of multiple small incremental doses of egg white solid. This is followed by 32-40 weeks of gradual dose escalation to a stable maintenance dose of egg white solid for at least 8 weeks. At approximately Week 44, participants are given an OFC using 5 grams of egg white solid to identify desensitized individuals. Participants and study staff are unblinded following this initial OFC. Maintenance egg OIT therapy is continued for an additional 1-3 years. Oral Food Challenges with 10 grams of egg white solid will be performed for participants on maintenance egg OIT at subsequent time points (approximately Week 96 and annually thereafter) to test for desensitization. If passed, a repeat OFC after being off therapy for 4-6 weeks will be performed to test for tolerance. An OFC to test for tolerance will use 10 grams of egg white solid and be followed by an open feeding of egg.

Participants receiving placebo during dose escalation and maintenance are given an OFC using 5 grams of egg white solid to test for desensitization at approximately 44 weeks. They are unblinded at that time, continue on an egg-restricted diet, and are followed until up to 2 years. These participants will only receive an OFC at a subsequent time point if their egg Immunoglobulin E (IgE) declines to be less than 2 kilounits of antibody per liter; this OFC will use 10 grams of egg white solid and be followed by an open feeding of egg.

At selected visits, blood and urine collection, physical examination, prick skin tests, and atopic dermatitis and asthma evaluations will occur.

Program/Contract:
ProgramContract
Immunobiology of Food Allergy and Its Treatment Immunobiology of Food Allergy and Its Treatment (CoFAR)
DOI: 10.21430/M3Q2O0X9Z5
Subjects: 55
Study PI, contact:
NameOrganizationSite
Wesley Burks Duke University Multiple sites
Stacie Jones Arkansas Children's Hospital Multiple sites
Publications:
Oral immunotherapy for treatment of egg allergy in children.. N Engl J Med. Jul 2012. doi: 10.1056/NEJMoa1200435. [Pubmed: 22808958]
Resources:
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT00461097?term=NCT00461097]
Assays:
Assay TypeNumber of Exp. Samples
ELISA 939
Flow Cytometry 2370
Clinical Assessments:None
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