T-Cell Therapy for Chronic Norovirus Infection

Inclusion Criteria: Participant Inclusion Criteria for NST Infusion: 1. Participants must meet one of the following criteria: 1. Recipient of prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells or single or double cord blood OR 2. Primary immunodeficiency disorder (as defined by clinical and laboratory evaluations)81 and have not undergone HSCT, OR 3. Recipients of solid organ transplant. 2. Documentation of chronic norovirus infection: a. Chronic norovirus infections will be defined as having consecutive positive norovirus stool tests (2 or more) spanning a minimum three-month period with attributable signs and symptoms of norovirus disease. 3. Participants receiving steroids for treatment of GVHD or for other reasons, dosage must have been tapered to \<0.5 mg/kg/day of prednisone (or equivalent) a minimum of 7 days prior to infusion. a. Treatment with enteral topical steroids such as Budesonide at standard doses may be continued if previously utilized but should not be newly initiated in the 3 months after NST therapy. 4. For participants who have undergone HSCT, participants must have stable donor chimerism within the 30 days prior to NST infusion. a. Stability will be defined as i. \>95% donor chimerism in CD33 and/or whole blood chimerism. OR ii. \>90% donor chimerism with \<5% change between subsequent tests separated by at least 1 week. 5. For recipients of solid organ transplants, participants must have stable graft function on maintenance immunosuppression, without evidence of rejection in the past 2 months prior to infusion, as defined by: a. Stability of relevant functional testing in the previous 2 months, defined as: i. Renal transplant: renal function ≥ grade 3 per the National Kidney Foundation K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease (2002) ii. Cardiac transplant: maintenance of LVEF \>40% iii. Lung transplant: lack of baseline oxygen requirement iv. Liver transplant: AST/ALT ≤3x upper limit normal and bilirubin ≤2x upper limit normal b. Donor-derived cell free DNA \<2x upper limits for assay in the previous 2 months, c. Stable donor-specific antibody profile in the previous 2 months. i. No increase in antibody titers between most recent testing in the previous 2 months and prior testing. 6. Karnofsky/Lansky score \>50 7. 3 months to 80 years of age at enrollment. 8. ANC ≥500/ul. 9. Hemoglobin ≥7.0g/dl (level can be achieved with transfusion). 10. Platelets ≥20 K/ul (level can be achieved with transfusion). 11. Bilirubin ≤2x upper limit normal. 12. AST ≤3x upper limit normal. 13. Serum creatinine ≤2x upper limit normal OR estimated GFR ≥30 ml/hr. 14. Pulse oximetry of ≥90% on room air. 15. Negative pregnancy test in female participant of childbearing age. 16. Written informed consent and/or signed assent line from participant, parent or guardian. Donor Inclusion Criteria: 1. Donors who have fulfilled eligibility as per United States Food and Drug Administration (FDA) regulations outlined in 21 Code of Federal Regulations (CFR) 1271 subpart C. This includes that donors have been deemed in good health by donor physician based on physical examination and laboratory testing. If a donor has been chosen for the transplant based on urgent medical need, that same donor will also be used for NST generation provided that there are no new reasons for ineligibility since the stem cell collection. 2. For third-party banking, donors must be between 2 to 35 years of age (females) or 2 to 40 years of age (males). 3. Donor or guardian of pediatric donor capable of providing informed consent. 4. Donor (related or unrelated) must have completed Infectious Disease (ID) testing up to 7 days before or after the collection of blood for NST manufacturing. The following tests will be performed: * HBsAg * HBc Antibody * HCV Antibody * HIV 1/2 Antibody * HTLV I/II Antibody * T. Cruzi Antibody (Chagas) * CMV Total Antibody * Syphilis (T. Pallidum IgG and IgM) * HBV, HCV, HIV Nucleic Acid testing (NAT) * WNV NAT 5. Female donors of childbearing age must have a negative pregnancy test and not be lactating. Exclusion Criteria: Participants Exclusion Criteria for NST Infusion: 1. Participants receiving biological or immunosuppressive monoclonal antibodies targeting T cells within 28 days prior to NST infusion, including ATG, Alemtuzumab, Basiliximab, Tocilizumab, Brentuximab, or other medications under this category as determined by the investigators. a) If alemtuzumab has been received within 6 weeks prior to NST infusion, plasma levels should be obtained to ensure drug clearance (≤0.16 pg/ml). 2. Participants who have received donor lymphocyte infusion (DLI), chimeric antigen receptor T cell infusion, or other experimental cellular therapies within 28 days prior to NST infusion. 3. Participants with SCID who have undergone α/β TCR depleted HSCT within the past 100 days post-transplant. 4. Participants who have received ruxolitinib or other JAK inhibitors within 7 days prior to NST infusion. 5. Participants with uncontrolled or progressing infections other than norovirus. Uncontrolled infections are defined as bacterial, fungal, or non-targeted viral infections with either clinical signs of worsening despite standard therapy, or chronic gastrointestinal symptoms that may be attributed to the uncontrolled infection. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. 1. For bacterial infections, participants must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to NST infusion and or no chronic gastrointestinal symptoms associated with this bacterial infection. 2. For fungal infections, participants must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to NST infusion. 6. Participants must not have other active gastrointestinal infections to which symptoms may be attributable, including parasitic infections (cryptosporidium, giardiasis), viral infections aside from norovirus (CMV colitis, rotavirus, adenovirus), or bacterial infections with C. difficile, Yersinia, Campylobacter, Salmonella, Shigella, or enteroinvasive or enterotoxigenic E. coli. a) Testing for unrelated gastrointestinal (GI) infections must be performed within 14 days prior to NST infusion, and must include: i. Crytosporidium/Giardia testing via antigen or PCR testing. ii. Stool viral testing for rotavirus and adenovirus via antigen or PCR testing. iii. Stool bacterial culture or PCR testing. iv. C. difficile toxin PCR. b) Determination of active infection versus chronic carriage/shedding will be made by the investigators and clinical providers and will depend on the presence of clinical symptoms corresponding with the timing of positive test results, presence of a clinical response to targeted therapy, and by histological or other testing if clinically indicated. 7. Participants with active and uncontrolled relapse of malignancy (if applicable). 1. Failure of primary engraftment is defined as failure to achieve platelet and/or neutrophil engraftment (ANC \<500/ul and/or platelets \<20 K/ul) following HSCT. 2. Secondary graft failure is defined as \<5% donor chimerism (CD3+ or CD34+) or permanent loss of neutrophil and/or platelet engraftment (ANC \<500/ul and/or platelets \<20 K/ul) at any time after primary engraftment. 8. Participants with symptomatic gastrointestinal conditions aside from norovirus, including active inflammatory bowel disease or graft versus host disease (grades 2 to 4). 9. Participants who have received a small bowel transplant. 10. Participants receiving checkpoint inhibitors within the previous 3 months prior to NST infusion, including nivolumab, pembrolizumab, or other related medications. 11. For SOT recipients, alteration in immunosuppression as follows: 1. Any intensification of immunosuppression (including but not limited to pulse dose corticosteroids or new biologic therapies) in the previous 2 months, 2. Alteration of maintenance immunosuppression (including changes in the number of agents or dosing goals) in the previous month. 12. Participants who have received enteral immunoglobulin, nitazoxanide, or other experimental therapies for norovirus infection within 28 days prior to NST infusion. 13. Co-enrollment in other trials is restricted, other than enrollment on natural history or observational studies. Study staff should be notified of co-enrollment as it may require the approval of the investigator or sponsor. Donor Exclusion Criteria: 1\. Donation of cells would pose a physical or psychological risk to the donor