Inclusion Criteria:

• - DONORS: Documented informed consent of the participant and/or legally authorized representative.

• - Assent, when appropriate, will be obtained per institutional guidelines.

• - DONORS: Age: 18 and above.

• - RECIPIENTS: Documented informed consent of the participant and/or legally authorized representative.

• - Assent, when appropriate, will be obtained per institutional guidelines.

• - RECIPIENTS: Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT.

• - RECIPIENTS: Age: 18 and above.

• - RECIPIENTS: Karnofsky performance score ≥ 70 or ECOG ≤ 2.

• - RECIPIENTS: Planned HCT for the treatment of the following hematologic malignancies: lymphoma (Hodgkin and Non-Hodgkin), myelodysplastic syndrome, acute lymphoblastic leukemia in first or second remission, acute myeloid leukemia in first or second remission, chronic myelogenous leukemia (in first chronic or accelerated phase, or in second chronic phase), chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis.

Patients with multiple myeloma are excluded.

• - RECIPIENTS: CMV seropositive.

• - RECIPIENTS: Planned related HCT with 8/8 (A, B, C, DRB1) high resolution human leukocyte antigen (HLA) donor allele matching.

• - RECIPIENTS: Conditioning and immunosuppressive regimens according to institutional guidelines are permitted.

Patients may receive myeloablative, reduced intensity, or nonmyeloablative conditioning.

• - RECIPIENTS: Total bilirubin ≤ 2 X upper limit of normal (ULN) (unless has Gilbert's disease) - RECIPIENTS: Aspartate aminotransferase (AST) ≤ 2.5 x ULN.

• - RECIPIENTS: Alanine aminotransferase (ALT) ≤ 2.5 x ULN.

• - RECIPIENTS: Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula.

• - RECIPIENTS: Left ventricular ejection fraction (LVEF) ≥ 50% Note: To be performed within 45 days prior to day 1 of protocol therapy.

• - RECIPIENTS: If able to perform pulmonary function tests: forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) (diffusion capacity) ≥ 50% of predicted (corrected for hemoglobin).

If unable to perform pulmonary function tests: oxygen (O2) saturation > 92% on room air Note: To be performed within 45 days prior to day 1 of protocol therapy.

• - RECIPIENTS: Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV)*, active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]) - If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed.

Viral load must be undetectable.

• - RECIPIENTS: Meets other institutional and federal requirements for infectious disease titer requirements Note: Infectious disease testing to be performed within 45 days prior to day 1 of protocol therapy.

• - RECIPIENTS: Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test.

If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

• - RECIPIENTS: Agreement by females and males of childbearing potential* to use an effective method of birth control (hormonal or barrier method) or abstain from heterosexual activity prior to study entry and for up to 90 days post-HCT.

• - Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

  Exclusion Criteria:

  - DONORS: Any prior transplant to day 1 of protocol therapy.

• - DONORS: Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy.

• - DONORS: Receipt of any vaccine (licensed or investigational) within 30 days prior to and after of the study vaccine.

• - DONORS: Unfit to undergo standard stem cell mobilization and apheresis e.g. abnormal blood counts, history of stroke, uncontrolled hypertension.

• - DONORS: Sickling hemoglobinopathy including hemoglobin S (HbSS), sickle cell trait (HbAS), hemoglobin sickle C disease (HbSC) - DONORS: Donors with impaired cardiac function are excluded.

Electrocardiography is routine for potential HCT donors over 60 years old and those with a history of heart disease. Subjects in whom cardiac function is abnormal (excluding 1st degree branch block, sinus bradycardia, sinus tachycardia or non-specific T wave changes) are ineligible for Triplex vaccination.

• - DONORS: Positive for HIV, active hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) - DONORS: Severe psychiatric illness.

Mental deficiency sufficiently severe as to make compliance with the donation procedure unlikely, and making informed consent impossible.

• - DONORS: Females only: Pregnant or breastfeeding.

• - DONORS: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.

• - DONORS: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics) - RECIPIENTS: Any prior investigational CMV vaccine.

• - RECIPIENTS: Experimental anti-CMV chemotherapy in the last 6 months.

• - RECIPIENTS: Prior allogeneic (allo) transplant for any condition.

• - RECIPIENTS: Live attenuated vaccines.

• - RECIPIENTS: Medically indicated subunit (Engerix-B for HBV; Gardasil for HPV) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections) - RECIPIENTS: Allergy treatment with antigens injections.

• - RECIPIENTS: Alemtuzumab or any equivalent in vivo T-cell depleting agent.

• - RECIPIENTS: Antiviral medications with known therapeutic effects on CMV such as valganciclovir/ganciclovir (GCV/VAL), foscarnet (FOS), cidofovir, brincidofovir (CMX-001), maribavir.

Acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV)

• - RECIPIENTS: Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment.

• - RECIPIENTS: Other investigational product - concurrent enrollment in other clinical trials using any investigational new drug (IND) drugs with unknown effects on CMV or with unknown toxicity profiles is prohibited.

• - RECIPIENTS: Other medications that might interfere with the evaluation of the investigational product.

• - RECIPIENTS: Diagnosis with autoimmune disease.

• - RECIPIENTS: Females only: Pregnant women and women who are lactating.

The risks of Triplex to pregnant women are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother. Breastfeeding should be discontinued if the mother is enrolled on this study.

• - RECIPIENTS: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.

- RECIPIENTS: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

PRIMARY OBJECTIVE:

• I. To determine whether multi-peptide CMV-modified vaccinia Ankara vaccine (Triplex) is safe and effective in protecting against CMV events defined as viremia requiring antiviral preemptive therapy (PET) or CMV end organ disease.

SECONDARY OBJECTIVE:

• I. To examine if Triplex vaccination of hematopoietic stem cell transplant (HCT) donors has an impact on CMV events.

OUTLINE: Donors are randomized to 1 of 2 arms. ARM I: DONORS: Donors receive Triplex vaccine intramuscularly (IM) on day 0 and then undergo stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study. ARM II: DONORS: Donors receive placebo IM on day 0 and undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study. After completion of study treatment, donors follow up on days 90, 180 and 365 after vaccination and recipients follow up on days 14, 28, 42, 56, 70, 100, 140, 180, 270, and 365 after transplantation.

Arms

Experimental: Arm I (Triplex vaccination)

DONORS: Donors receive Triplex vaccine IM on day 0 and then undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study.

Placebo Comparator: Arm II (Placebo)

DONORS: Donors receive placebo IM on day 0 and undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study.

Interventions

Procedure: - Allogeneic Hematopoietic Stem Cell Transplantation

Undergo HCT with donor peripheral blood stem cells

Procedure: - Biospecimen Collection

Undergo blood sample collection

Drug: - Granulocyte Colony-Stimulating Factor

Undergo stem cell mobilization with G-CSF

Drug: - Hematopoietic Cell Transplantation Conditioning Regimen

Receive pre transplant conditioning

Biological: - Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Given IM

Procedure: - Pheresis

Undergo apheresis

Drug: - Placebo Administration

Given IM

Drug: - Stem Cell Mobilization Therapy

Undergo stem cell mobilization with G-CSF