Project description:Transcriptional profiling of HBV-naïve subjects after vaccination against Hepatitis A/B viruses, Diphtheria/Tetanus toxoids and Cholera.
Project description:Mechanisms of poor responses to vaccines remain unknown. Hepatitis B virus-naïve elderly subjects received three vaccines, including a vaccine against hepatitis B virus (HBV). Transcriptomic profilling of blood collected pre-vaccination and post-vaccination was performed in order to identify candidate biomarkers of antibody response to the different vaccines.
Project description:Background: Drugs given to treat cancer (chemotherapy) can weaken the human immune system. But it can also become weaker because of aging. Interleukin (IL)-7, a molecule produced naturally in the body, can help improve the function of the immune system. Researchers want to study the effects of IL-7 on immune system function in two different groups of older people. One group will be people who have received vaccines before IL-7. The other group will be people who have received Vaccines after IL-7.
Objectives: To evaluate the effect of IL-7 on the immune system responses to vaccines in older people following chemotherapy.
Eligibility: People at least 60 years of age who have recently finished chemotherapy for breast, colon, or bladder cancer.
Design:
* People in the study will be screened with a physical examination, medical history, and blood tests. Other screening tests, such as tumor imaging, may also need to be performed.
* Everyone will receive a series of five different vaccines commonly used to prevent diseases. We will compare the responses of people in Sequence 1 who will receive vaccines before IL-7 with the responses of people in Sequence 2 who received the same vaccines after IL-7.
* The vaccines will be given randomly in two Arms at different times.
* Arm 1: diphtheria and tetanus, polio, pneumonia (with two booster shots), hepatitis B (with two booster shots), and hepatitis A (with one booster shot),
* Arm 2: hepatitis A (with one booster shot), hepatitis B (with two booster shots), pneumococcal (with two booster shots), diphtheria and tetanus, polio, pneumonia (with two booster shots)
* There are 5 vaccines to be given to each subject, following one of two randomly assigned sequences of vaccine administration (Sequence 1 or Sequence 2).
* The first vaccine arm contains the two diphtheria protein containing vaccines tetanus and diphtheria (Td) and pneumococcal conjugate 13 (PCV13) and polio. The second vaccine arm contains the Hepatitis A and Hepatitis B vaccines. Subjects will either get tetanus, diphtheria, polio, and pneumonia vaccines before IL-7 therapy (Sequence 1) or hepatitis A and hepatitis B vaccines before IL-7 therapy (Sequence 2). The response to vaccines will be evaluated 4 weeks after vaccination. This will be followed by IL-7 therapy, then administration of the other group of vaccines. Therefore, subjects on both arms will receive the same set of vaccines, just at different times with respect to IL-7 therapy.
Project description:Mechanisms of poor responses to vaccines remain unknown. Hepatitis B virus-naïve elderly subjects received three vaccines, including a vaccine against hepatitis B virus (HBV). Pre-vaccination high dimensional analyses of blood using transcriptional profiling and flow cytometry revealed that subjects having increased memory B cell frequencies and higher expression of genes downstream of B cell receptor signaling responded more strongly to the HBV vaccine whereas subjects having higher expression of inflammatory related genes and greater numbers of activated innate immune cells showed a weaker response to this vaccine. The heme-induced response was associated with the poor response to the hepatitis B vaccine. Transcriptional profiling and flow cytometry results were validated in a distinct set of elderly subjects with accuracy greater than 60%. Our study is the first that identifies baseline predictors of responses to vaccines in a population of subjects known to be highly susceptible to infections.
Project description:Short Description: This study contains 7 RRBS samples, including 3 ex vivo CD4+ Trm (2 x spleen and 1 x bone marrow) and 4 blood tetanus (TT) and measles (Me) antigen-reactive memory CD4+ cells before and one day post DTaP (diphtheria-tetanus-pertussis) and MMR (measles-mumps-rubella) vaccination, respectively (1 x tetanus D0, 1 x tetanus D1, 1 x measles D0, 1 x measles D1).
Technology: Illumina HiSeq 2500
Filetype: fastq format
Project description:Metabolomics analysis was performed on 112 serum samples that were collected in India at baseline (before Cholera vaccination) and 28 days after Cholera vaccination under the Population Genetics Project (National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) contract HHSN2004000676C). The 112 samples were selected based on titer results which indicated subjects who were either high responders or low responders to the vaccination. 950MHz 1H NMR spectra were acquired for the 112 serum samples.
Project description:Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. We extracted RNA from blood samples before, and 6 weeks after, vaccination to analyse the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analysed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. We found very few transcripts to alter systematically. Those that did mainly belonged to the interferon (IFN) signalling pathway. We scrutinized this pathway as well as the interleukin pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. In conclusion, the transcriptome changes following DTP booster vaccination were subtle, but it is possible to identify sub groups that deviate from each other, mainly in the IFN response. Microarrays (Human Exon 1.0 ST Arrays (Affymetrix )) were used to compare the gene expression alteration following DTP-vaccination in 18-19 months old West African girls. The gene expression analysis was based on RNA from venous blood. The blood was drawn immediately before DTP-vaccination (baseline sample) and 6 weeks after (42 -50 days, post-vaccination sample) in a total of eight girls
Project description:Hepatitis B virus (HBV) is an enveloped, coated, non-cytopathic and hepatotropic partially double-stranded DNA virus in the family Hepadnaviridae genus Orthohepadnavirus. Despite significant progress in the availability of safe vaccines and antiviral therapies against HBV, it still affects approximately 257 million people worldwide and is responsible for about 887,000 deaths per year around the world [4]. HBV infection, which are associated with acute and chronic liver failure responses to viruses attacked the liver, can result in inactive carrier state, chronic hepatitis, or fulminant hepatitis and put them at high risk to develop advanced liver fibrosis and cirrhosis, and even hepatocellular cancer. Many viral factors, which could affect the disparity of clinical outcomes or disease prognosis during chronic HBV infection, have been reported in previous studies; among them, the viral genotype, as well as HBV mutations ascribing the virus to a certain phenotype, was reported to be the most important factor influencing viral pathogenesis, including the change of host immune recognition, the enhanced virulence with increased HBV replication and the facilitation of cell attachment or penetration.
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection. Transcriptome profiling by DNA microarray of Huh7.5.1 cells transduced to express NTCP.
Project description:To identify the sncRNAs related to HBV-ACLF, we performed small RNA-seq in plasma exosomes collected from 3 normal subjects, 4 chronic hepatitis B (CHB) patients with flare and 6 HBV-ACLF patients in the discovery cohort.