Core C: Infectious Disease Core

Massachusetts General Hospital, Boston MA

Investigators

Abstract

CORE C: INFECTIOUS DISEASE ABSTRACT Microbiological safety is central to clinical xenotransplantation. The Infectious Disease Core will provide microbiological surveillance of multi-GE pigs and non-human primate (NHP) xenograft recipients using advanced metagenomic techniques. We will provide expertise to complement veterinary support. Quantitative next generation sequencing (NGS) will be provided on cell-free DNA and RNA for panels of known and common pathogens of swine and NHP and nontargeted sequencing for unknown and unexpected organisms. Based on experience with clinical and preclinical xenotransplantation, the core will provide data on viruses, bacteria, fungi, and parasites for which sequence data are available (>20,000). The NGS approach will also provide potential pathogen discovery to advance screening for clinical xenotransplantation where knowledge of potential porcine pathogens is limited. We will apply screening using hybrid capture for viral target enrichment for Whole Transcriptome Sequencing using a Comprehensive Viral Capture Panel (targeted and non- targeted) to validate this technique and increase assay sensitivity via detection of viruses not found by standard NGS. Samples will be obtained from xenograft recipients in each Project under either standard or costimulatory blockade-based immunosuppression. These data will be provided to Projects as a basis for refining management of antimicrobial prophylaxis, adjusting intensity of immunosuppression, and provide sequences for spatial transcriptomics probes in the pathology core to further document the presence of infection in specific xenograft tissues and cells(B).