Immune Response

The aim of this observational study is to characterize the urinary replication of BK polyomavirus (BKV) in kidney transplant recipients. Although BKV reactivation after transplantation is well established, the origin of the replicating virus remains uncertain. Current evidence suggests that BKV detected in recipients may originate either from the transplanted kidney (donor-derived) or from viral reactivation in the recipient. The evaluation of new biomarkers to predict BKV replication are needed. This study seeks to address the following key questions: * Origin of the replicating virus: Is the BKV detected in the recipient identical to the virus originating from the donor kidney? * Host immune response and viral genotype: Is there an association between the recipient's immune response and the genotype of the replicating BKV? * Differences in immune response according to viral replication profile: Does the immune response differ between patients presenting isolated BKV viruria and those with both viruria and viremia? * Can new biomarkers help predict BKV replication and viremia? Patients will be grouped according to their BKV replication profile: Group 1: patients with BKV viruria without viremia Group 2: patients with both BKV viruria and viremia Comparisons between these two groups will help identify whether different viral genotypes or immune responses are associated with systemic dissemination (viremia). Kidney transplant recipients will be included if they present BKV viruria during their post-transplant follow-up. Additional blood samples will be collected during scheduled follow-up visits at the university hospital. These visits are part of routine clinical care, and no extra visits will be required specifically for the study.

296 million people worldwide are infected with the hepatitis B virus (HBV), despite the existence of an effective prophylactic vaccine. Current treatments (nucleoside analogues and pegylated interferon-α) do not prevent chronic hepatitis B (CHB) patients from developing liver fibrosis or hepatocellular carcinoma. Vaccination is the best way to prevent HBV infection. The first generation of plasma-based vaccines, introduced in the 1980s, has now been superseded by protein vaccines, which are the only ones authorized in France. They are safe and effective. After an initial series of three out of four doses, protective levels of antibodies to the HBV surface antigen (anti-HBsAg; ≥10 IU/mL) are achieved in over 95% of infants, children and young adults. HBV antigen (Ag)-specific CD4+ and CD8+ T lymphocytes play a major role in the control of HBV infection, contributing to viral clearance and the pathophysiology of acute hepatitis B. However, during HBC, these HBV-specific T cells develop a dysfunctional phenotype and become 'exhausted'. T lymphocytes directed against surface protein antigens (HBsAg) are the most affected by depletion mechanisms - these disappear completely in chronically infected patients, suggesting an important role for these T lymphocytes in infection control. Interestingly, recent studies of rare patients undergoing functional recovery from chronic infection following antiviral treatment have shown a re-emergence of T lymphocytes directed against HBsAg, confirming the importance of these cells in controlling viral replication. Although the protection induced by hepatitis B vaccination has mainly been attributed to the humoral response, a few studies have documented the presence of HBsAg-specific T lymphocytes. These could contribute to the maintenance of a long-term post-vaccination humoral response. The aim of this study is therefore to determine the frequency of healthy individuals receiving HBV vaccination who have a detectable HBsAg-specific T-cell response post-vaccination. We will also study the potential correlation between the frequency of HBsAg-specific T lymphocytes and the level of serum anti-HBsAg antibodies, and we will finely characterize the functional phenotype of these cells using cutting-edge methods and technologies (spectral cytometry, sequencing of mRNA and TCRs). These data will contribute to a better understanding of the biological mechanisms associated with HBV vaccine-induced protection.

The goal of this clinical trial is to learn whether a high- and low-dose radiotherapy regimen followed by anti-angiogenic TKI and anti-PD-1 antibody therapy works to treat advanced metastatic colorectal cancer. It will also evaluate long-term survival outcomes and explore potential biomarkers associated with tumor response and immune modulation. The main questions it aims to answer are: Does the high- and low-dose radiotherapy regimen followed by sequential anti-angiogenic TKI and anti-PD-1 therapy improve the objective response rate (ORR) in patients with advanced metastatic colorectal cancer? What are the disease control rate (DCR) and survival outcomes following this treatment strategy? Are tumor response and long-term survival associated with specific biomarkers related to systemic immune modulation induced by radiotherapy to different metastatic organs? How does this radiotherapy pattern affect tumor immune infiltration in metastatic lesions? This is a single-arm, single-center, prospective Phase II clinical study designed to evaluate the efficacy of a high- and low-dose radiotherapy regimen targeting metastatic lesions followed by sequential anti-angiogenic TKI and anti-PD-1 antibody therapy in patients with advanced metastatic colorectal cancer. Participants will: Receive high- and low-dose radiotherapy to metastatic lesions. Subsequently receive anti-angiogenic TKI combined with anti-PD-1 antibody therapy. Undergo regular clinical assessments and imaging evaluations to determine tumor response. Provide blood and tumor samples for biomarker and immune infiltration analysis. Be followed for survival outcomes and disease progression.

Introduction: Vaccination is a powerful weapon in the fight against infectious diseases, which has led to dramatic reduction in mortality and complications from some diseases. In this respect, vaccination is a real worldwide public health challenge (WHO). Thus, vaccine research benefits from an exponential development of knowledge in immunology and biotechnology. In particular, the advent of recent tools ("omics", new cytometric assays) and the description of new categories of immune cells (Tfh, BReg...) have revolutionized the characterization of immune responses, particularly post-vaccination. To study of the immune response following vaccination remains essential in order to define the immunological correlates to vaccine protection. This response also varies according to parameters related to the vaccine (type, adjuvant, dose, regimen…) and to the vaccinated host (genetics, age, morbidity, treatment …). Analyzing with new generation immune assays, new data on immunological responses post-vaccination from a clinical cohort is therefore essential to better define these correlates. Objective: To develop new vaccines (HIV, emerging infectious diseases) the investigators use a "System vaccinology" method to decipher the mechanisms of immune responses set up against vaccines currently being developed or marketed, specifically in specific populations (patients with primary immune deficiency, sickle cell patients, solid organ transplanted patients, COPD). Method: Description of the genetic, molecular and cellular mechanisms of the immune response to vaccines recommended for adults, in particular influenza and pneumococcal vaccines, but also other mandatory vaccines (MMR,...) or vaccine for travelers (yellow fever, ...) as part of routine care in different population categories (healthy subjects, HIV+ subjects, COPD patients, …), using qualitative and quantitative immunological assays: transcriptional analysis of the dynamic innate immune response, analysis of the lymphocytes B \& T responses (phenotype, repertoire analysis, functional analysis including T reg and TFH populations, antibody response), genetic analysis in the context of primary immune deficiencies) Conclusion: The data generated will allow the best possible analysis of vaccine responses according to vaccines and vaccinated populations, providing important information for the research developed within the department.