Clinical Research Directory

Longitudinal Tracking of Bone Marrow Plasma Cell Responses to Licensed Human Vaccines

This study is being done to understand and measure how the immune system responds to and remembers different types of vaccines. To do this, four vaccines approved by the U.S. Food and Drug Administration (FDA) will be given simultaneously to participants. Participants will be volumteers who are healthy adults (18 years old or older) and willing to receive the yearly trivalent inactivated influenza vaccine (TIV), the tetanus, diphtheria, and acellular pertussis vaccine (Tdap), the nonvalent HPV (HPV) vaccine, hepatitis A virus (HAV) vaccine and undergo study procedures. Procedures will include: * medical history relevant to the study, including medications and vaccines received. * Vitals (blood pressure, pulse) and temperature * Height and weight. * Physical exams. * Receive the TIV, Tdap, HPV, and HAV vaccines. * Blood samples collected for immunologic tests and genetic analysis. * Donate bone marrow by needle aspiration at a maximum of seven visits. * Complete memory aid every evening for 7 days after vaccination Optional Procedures include: * Donate bone marrow core biopsies at the same visits * Ultrasound of lymph nodes and fine needle aspirates of lymph nodes in both arm pits at a maximum of eight separate visits There will be a screening visit and and a Day 1 where vaccinations will occur and subsequent visits at Day 8, Day 14, Day 29, Day 57, Day 121, Day 181, Day 366, Day 546, and Day 731. At each of these visits health status, vital signs and blood collection will occur. A bone marrow aspirate and lymph node aspirate will be collected at screening. The six additional bone marrow aspirates will be repeated at D29, D91, D181, D366, D546, and D731. The optional bone marrow core biopsy will also be repeated at that time. Up to seven separate visits will be scheduled for the follow-up lymph node aspirates (D29, D57, D91, D181, D366, D546, and D731) Study participation will be 24 months.

A Trial of SHR-2173 in Healthy Volunteers

The purpose of this study is to assess safety, PK, Pharmacodynamic and immunogenicity profile of a single dose of SHR-2173 in healthy participants

Impaired Type I IFN Immunity Due to Autoantibodies or a Genetic Defect: a Prospective National Cohort

The major role of human genetic factors in the immune response to infections is now well established, particularly for viral infections. In the context of the COVID-19 pandemic, the following results have identified 1) several inborn errors of immunity (IEI) affecting the response or production of type I interferons (type I IFNs) in around 4% of adult patients with severe clinical disease, and 2) the presence of type I IFN-neutralizing autoantibodies (auto-Abs) in around 15% of severe cases, and 20% of deaths. The investigators would like to carry out a longitudinal immunological and clinical follow-up study on a prospective cohort of patients with either a genetic defect affecting the type I IFN-dependent immune response, or anti-IFN-I auto-Abs, to monitor the incidence of infectious and/or autoimmune events in these individuals, the evolution of neutralizing power, and the kinetics of auto-Abs. This should lead to a better understanding of the prevention and management of these patients. The research design is a national multicenter prospective cohort of adults with 1) anti-IFN-I auto-Abs or 2) IEI- IFN-I, with follow-up from 1 to 4 years. These individuals may be: 1) patients who have or have had clinical disease (related to COVID-19, other viral infections, autoimmune disorders); or 2) "healthy" participants (e.g. blood donors, relatives of an IEI patient). Follow-up will include: * yearly visits to the Clinical Investigation Center (CIC) or a clinical department with blood sampling; * specific visit in case of hospitalization for infectious events or adverse effects of vaccination, exacerbation or new diagnosis of auto-immune disease, new diagnosis of cancer, or SARS-CoV-2 infection whether or not patients are admitted to hospital, with blood sampling. In addition, a retrospective "passive" follow-up will be implemented through matching with the data from the SNDS (National Health Data System), in order to collect clinical events of and healthcare resource consumption. Moreover, matching with controls adults from the national CONSTANCES cohort, not carrying auto-Abs against type I IFNs nor IEI-IFN-I, will be performed. (ratio 3:1; matching on age (+/- 5 years), gender and geographic region of recruitment). Individuals under long-lasting immunosuppressive or immunomodulatory drugs will not be eligible. Follow-up of controls, which will be carried out as part of the CONSTANCES cohort, will include web-based questionnaires, every 12 months, in addition to linking with SNDS data as already done in this cohort. Inclusion visit: After signing the consent form, the following tests will be performed: * Demographic characteristics (sex, age, country of birth) * Medical history from participant and family member(s) including infectious and auto-immune diseases, cancers and vaccination status and side effects * Blood samples for: * full blood cell count; * classical autoimmune investigations (anti-nuclear, anti-ENA, native anti-DNA, anti- thyroid antibodies, rheumatoid factor); * immunophenotyping\*; * auto-Abs against type I IFNs, other cytokines\*, or other target proteins\* (dosage and neutralization activity); * Genetic explorations by whole-exome or whole-genome sequencing\*; * Biobanking (DNA, plasma/sera; cryopreserved peripheral blood mononuclear cells (PBMCs). * these biological analyses will be carried out as part of dedicated COVIFERON RHU5 workpackages. In addition, vaccination against SARS-CoV-2 and influenza will be offered to these subjects as a priority, as part of their usual care. Follow-up visits : Annual visits to the CIC : * Medical history since last visit, including infectious, auto-immune and oncologic events, vaccination status and side effects * Blood samples for: * full blood cell count; * classical autoimmune investigation (anti-nuclear, anti-ENA, native anti- DNA, anti-thyroid antibodies, rheumatoid factor); * immunophenotyping; * Auto-Abs against type I IFNs, other cytokines, or other target proteins (dosage and neutralization) * Biobanking (DNA, plasma, cryopreserved peripheral blood mononuclear cells (PBMCs)) Additional specific visit in the event of a clinical event of interest, at any time during follow-up: * In case of SARS-CoV-2 infection, whatever the severity of the disease: blood sampling for determination and neutralization of type I anti-IFN autoAbs, CBC, and biobanking (plasma and PBMC) and teleconsultation with the CIC in charge of patients, as soon as possible. * In the event of hospitalization for infectious events or exacerbation or new diagnosis of an auto-immune disease: blood sampling for determination and neutralization of anti-IFN-I autoAbs, CBC, and biobanking (plasma and PBMCs) and collection of the hospitalization report in the case report form on a dedicated page.

A Clinical Study to Evaluate the Safety and Efficacy of Anti-human CD 7 CAR-NK Cell Injection in Subjects With Relapsed and Refractory CD7-positive Hematological Malignancy

This study is a single-arm, open-label, dose-escalation clinical trial to explore the safety, tolerability, pharmacokinetics and pharmacodynamics characteristics of the drug; The efficacy of the study drug in subjects with relapsed/refractory CD7-positive hematological malignancies, and the expression of B cells, T cells, and NK cell subtypes in peripheral blood were preliminarily observed. At the same time, explporing the distribution of anti-human CD7 CAR-NK cells in tumor tissues after administration of anti-human CD7 CAR-NK cell injection, and evaluating the immunogenicity of anti-human CD7 CAR-NK cell injection . To evaluate the correlation between the proportion of CD7-positive tumor cells and the safety and efficacy of anti-human CD7 CAR-NK cell injection and the evaluation. To explore the pharmacokinetics (PK) and pharmacodynamics(PD) characteristics of bone marrow in Chinese medicine.

BmemHLA : Origins of the Heterogeneity of the Anti-HLA Memory B Cells in Kidney Transplantation

This study will describe the transcriptomic and phenotypic characteristics of anti-HLA memory B cells by comparing five groups of patients awaiting renal transplantation: patients with a single history of pregnancy, transfusion or failure of a first renal transplant requiring transplantectomy within 3 months of transplantation, or after 3 months, and patients without an immunizing allogeneic event. The hypothesis is that these five contexts induce different types of memory B cells with different modalities of reactivation and post-transplant pathogenicity.

SHR0302 Combined With PD-1/PD-L1 Inhibition for Treatment naïve or Acquired Resistant to Immunology NSCLC

Recent studies showed that the dysregulated activation of the JAK/STAT pathway, which leads to the prolonged release of IFN-γ, is a significant contributor to the resistance to immune checkpoint inhibitors in cancer immunotherapy. Preclinical and clinical studies have demonstrated that the combination of JAK inhibitors with PD-1 immunotherapy can reverse or delay onset of immunotherapy resistance by modulating the JAK/STAT pathway in Hodgkin's lymphoma and non - small cell lung cancer (NSCLC). SHR0302, being a highly selective JAK1 inhibitor, has shown excellent clinical benefits by effectively inhibiting the JAK/STAT pathway, leading to its approval for the treatment of Ankylosing Spondylitis in China. Preclinical studies also show that the combination of SHR0302 and PD-L1 inhibitor has synergistic potentials for anti-tumor effect in resistant to-immune checkpoint blockade patients. Thus, we conducted a phase 2 clinical trial evaluating SHR0302 combined with PD1/PD-L1 inhibitors as treatment-naïve or acquired resistant to first-line checkpoint inhibitor resistant NSCLC patients.

Immunomodulation During Pregnancy

The goal of this observational study is to learn about the effects of low dose aspirin in immunity Pregnant women taking aspirin for other reasons (preeclampsia prevention) will be studied. The main question it aims to answer is: evaluate the effect of LDA on the modulation of innate immunity cells (NK cells, monocytes, γδ T cells) and/or acquired immunity (B and T lymphocytes, Treg cells, Th cells). Participants already taking intervention A as part of their regular medical care for RA will answer online survey questions about their joint pain for 5 years.

Aspirin and Neutrophils in Preeclampsia

The exact mechanisms by which aspirin prevents the development of preeclampsia in high-risk patients are currently not fully known. Furthermore, a small proportion of high-risk patients who are on low-dose aspirin (LDA) still go on to develop preeclampsia (PE). This longitudinal observational study will assess the immune profile in participants who are taking low dose aspirin (LDA) in pregnancy. As part of routine care, patients at high risk of developing preeclampsia are treated with LDA from 16 weeks gestation. The study will be conducted at Barts Health National Health Service (NHS) Trust. The study population will comprise of 2 groups of participants: 1. Those who respond to LDA and do not develop preeclampsia (responders) 2. Participants who do not respond to LDA and develop preeclampsia (non responders) Participants will be consented at their booking appointment. Participants will be eligible if they have a singleton pregnancy and are aged over 18 years. They will have an additional blood sample taken at 12, 20, 28 and 36 weeks gestation. The blood samples will be tested to assess immune cell function, metabolism and genetics. This will identify cumulative changes in immunobiology at key time points in pregnancy.

Effects of Resistance Training and Supplementation in Elderly: Cardiorespiratory and Metabolic Variables

Aging causes losses in strength, lean mass, and cardiovascular health in the elderly due to metabolic changes and alterations in body composition. To investigate whether nutritional interventions and physical training can mitigate these effects, a randomized clinical trial will be conducted at the Evangelical University of Goiás with elderly individuals aged 60 to 85. Participants will be divided into four groups: control, protein supplementation, physical training, and a combination of both. The study will last for 12 months, with evaluations every four months, covering cardiovascular, pulmonary, immunological, renal, muscular, and hematological parameters. The analyses will seek statistical significance, and it is expected that the interventions will significantly improve the participants\' health.

The Premature Gut Microbiome and the Influence on Neonatal Immunity, Brain Development and White Matter Injury

Recent advances in neonatal intensive care have dramatically increased the survival rate of extremely premature infants but the number of survivors with severe morbidity and lifelong neurodevelopmental impairment remains high. Perinatal white matter injury is the predominant form of brain injury in premature infants, often leading to adverse neurodevelopmental outcome. Intrauterine and neonatal infection and inflammation have been identified as major risk factors of neonatal brain injury. The fragile gut microbiome of premature infants seems to play an important role in health and disease as distortions of the microbiome occur prior to sepsis and necrotizing enterocolitis. Furthermore, the close link of the gut microbiome to neurological and psychiatric diseases in animal models suggests that the microbiome may influence brain maturation and development in preterm infants. Recent studies have underlined the importance of regulatory T cells as well as γδ T cells in brain injury, which can be directly influenced by the gut microbiome. It is therefore likely that an underdeveloped or distorted gut microbiome affects host immune response and may be a risk factor for neurodevelopmental disabilities in extremely premature infants who are already challenged by the unphysiologic early extrauterine environment after premature birth which affects maturation of the gut microbiome and immune system as well as neurophysiological maturation alike. Therefore, the overarching aim of the PreMiBraIn study is to elucidate the role of the gut-immune-brain axis on neonatal brain injury and its impact on long-term neurodevelopmental outcome of extremely premature infants. The study cohort will consist of a total of 60 extremely premature infants with a gestational age \< 28 weeks and birth weight \< 1000 grams. The investigators seek to characterize the orchestrated dynamics of the maturation of the gut microbiome and the subsequent impact on maturation of innate and adaptive immune mechanisms as well as neurophysiological maturation and neurodevelopmental outcome. Furthermore, the investigators will assess the value of the microbiome as a prognostic indicator for neonatal brain injury as well as short- and long-term neurodevelopmental outcome of extremely premature infants. This goal will be achieved by state-of-the-art techniques using 16s rRNA gene sequencing of the gut microbiome, holistic analysis of T cell biology using flow cytometry, whole transcriptome analysis and proteomics as well as neurophysiological measurements (amplitude-integrated EEG, near-infrared spectroscopy, visual evoked potentials) and cranial MRI of extremely premature infants. Short- and long-term neurological outcome will be investigated using Bayley Scales of Infant Development, Third Edition at one and two years corrected age, and Kaufmann-Assessment Battery for Children at five years of age. The investigators expect to find microbiome signatures that are predictive for later neurodevelopmental disabilities which may then be used for early screening and intervention and may suggest personalized therapeutic options. The prospects of precision medicine targeting the gut-immune-brain axis in extremely premature infants hold the opportunity to improve the overall outcome of these high-risk patients.