Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

Pneumococcal Vaccine Study: This is a study designed to develop a detailed transcriptional and cellular profile of the immune response to pneumococcal vaccination with conjugated and non-conjugated polysaccharide vaccines in the senescent immune system of older adults. In this study, 39 healthy adults ages 60 and older that have never received pneumococcal vaccination, have been randomized to receive Prevnar 13 (Pfizer), a conjugated 13-valent vaccine or Pneumovax 23 (Merck), a non-conjugated 23-valent vaccine. Four (4) study visits occurred over 70 days at Day -7 (baseline), day 1, day 10 and day 60 (± 5d) post vaccination.Bulk RNA-sequencing data are available on the 4 time points for 31 of the participants and 1 replicate. ATAC-Doublet Detector Study: We generated single nucleus ATAC-seq (snATAC-seq) data from PBMCs of 2 baseline blood samples from the pneumococcal study. Generated data was then used to benchmark a novel computational method for detecting multiplets in snATAC-seq data, namely, AMULET (https://github.com/UcarLab/AMULET). Multiplets confound downstream analyses by introducing combined epigenomic profiles from 2 or more cells/nuclei. AMULET detects multiplets by using unique snATAC-seq data features that allow it to reliably use read counts to detect multiplets for their removal from data analyses. ]]>
Pneumococcal vaccine study Inclusion Criteria: Able and willing to provide written informed consent Male or Female, 60 years of age or older Willing to receive pneumococcal vaccination with Prevnar 13 (Wyeth/ Pfizer) or Pneumovax 23 (Merck), as randomly assigned Available to attend 6 study visits over 67 days (Visit 7 is optional at Day 365-720) Exclusion Criteria: Previous pneumococcal vaccination with Prevnar 13 or Pneumovax 23. History of anaphylactic/anaphylactoid or severe allergic reaction to any component of Pneumovax 23, Prevnar 13 or any diphtheria toxoid-containing vaccine. Established diagnosis of diabetes History of receiving Zostavax (shingles vaccine) within previous 4 weeks. (Study entry may be delayed to satisfy a 28-day interval between vaccinations) Known history of any of the following co-morbid conditions: Malignancy (participants without a recurrence in the last 5 years will be allowed) Congestive Heart Failure Cardiovascular Disease (unstable ≤ 6 months*) Kidney disease Renal failure Impaired hepatic function Autoimmune disease such as: Rheumatoid Arthritis, systemic lupus erythematosus (SLE), Inflammatory Bowel Disease, etc. Use of medicines during past 6 months known to alter immune response such as high-dose corticosteroids HIV, AIDS or other Immunodeficiency Recent (≤ 3 months) trauma or surgery Current substance and/or alcohol abuse ]]>