Project description:End-stage renal disease patients experience uremia-driven immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, motivates an examination of immune response to the COVID-19 mRNA-based BTN162b2 vaccine. We performed gene expression profiling by RNA-seq across 6 time points to assess vaccine response in healthy controls and hemodialysis patients over time.
Project description:We longitudinally profiled plasma proteomes in 54 adults vaccinated with the BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (Oxford-AstraZeneca) vaccines. Blood was collected pre-vaccination (V0) and 1-7 days after the 1st doses (BNT162b2 or mRNA-1273, V1) to assess innate and early adaptive responses. We identified key differences in the immune responses induced by the ChAdOx1-S and BNT162b2 vaccines that were correlated with subsequent antigen-specific antibody and T cell responses or vaccine reactogenicity. We observed that vaccination with ChAdOx1-S but not BNT162b2 induced a memory-like response after the first dose, which was correlated with the expression of several proteins involved in complement and coagulation. The COVID-19 Vaccine Immune Responses Study (COVIRS) thus represents a major resource to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.
Project description:Individuals with comorbidities, such as chronic kidney disease and hemodialysis patients (HDP), are particularly susceptible to severe COVID-19 and to its complications. Furthermore, their immune response to vaccines is impaired, requiring tailored vaccination strategies. In this study, we investigated through transcriptomic profiling the immune response heterogeneity of HDP vaccinated with two doses of mRNA BNT162b2 vaccine. Transcriptomic analyses were conducted in peripheral blood mononuclear cells (PBMC) collected from HDP and healthy controls (HC) before and 7 days after each dose. The HDP were stratified into high- and low-responders based on their humoral response after the second dose. Significant differences in gene expression related to B cell abundance and regulation, CD4 T cell proliferation, and inflammation pathways were observed at baseline and day 7 between HDP-low responders and HC, while the HDP high-responders displayed an intermediate expression profile for these genes. Results were consistent with the known immunologic alterations occurring in HDP cohorts related to lymphopenia, chronic inflammation, and dysregulated proliferation of CD4+. Our analyses identified an early transcriptional signature correlated with a diminished immune response in HDP low-responders, highlighting the importance of conducting a characterization of immunocompromised cohorts.
Project description:COVID-19 mRNA vaccines generate high concentrations of circulating anti-Spike antibodies and Spike-specific CD4+ T cells following prime-boost vaccination. It is not yet clear if vaccine-induced CD4+ T cell responses in the draining lymph node contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we found large populations of Spike-specific CD4+ T follicular helper cells in the draining lymph node. A broadly immunodominant HLA-DPB1*04-restricted response to Spike166-180 composes one of the largest populations of T follicular helper cells in individuals with this allele, which is itself among the most common HLA alleles in the human population. Spike-specific T follicular helper cells are present in the lymph node 30 days after vaccine boost and persist in some individuals more than 170 days. Collectively, our results underscore the key role that robust T follicular helper cell responses play in the establishment of long-term immunity in this very efficacious human vaccine.
Project description:Adult-onset Still’s disease (AOSD) patients represent a population for which vaccination can induce disease flare1. The COVID-19 pandemic vaccination programs presented these patients and their health care providers with a critical decision. Previously it has been described that AOSD patients can experience disease flare with COVID-19 vaccination but no one has yet reported their immune transcriptional and antibody response. Here we present the transcriptional response and anti-spike antibody profile of a 58-year-old male after vaccination with BNT162b2 who experienced a mild AOSD flare following the second vaccine.
Project description:Bulk mRNA sequencing of whole blood from health-care professionals aged 28-65 years was perfomed in samples collected before and three days after the second dose of BNT162b2, in order to analyze the human immune response to dual mRNA immunization with the mRNA BNT162b2 vaccine.