The main purpose of the study is to evaluate the efficacy and safety of mRNA-1647 compared to placebo to prevent first clinically significant cytomegalovirus infection (CS-CMVi) in the period following cessation of CMV prophylactic treatment (for example, letermovir) on Day 100 post-HCT through Month 9 post-HCT.

Inclusion Criteria:

• Receipt of an allogeneic HCT.
• CMV-seropositive, defined as a documented positive test for anti-CMV IgG.
• High-risk for CMV: HCT from related, unrelated, or haploidentical donor with post-transplant cyclophosphamide for graft-versus-host-disease (GVHD) prophylaxis; or HCT from related or unrelated donor with at least one mismatch at any of the following human leukocyte antigen (HLA) gene loci (HLA-A, B, C, and DRB1); or HCT from related or unrelated donor with myeloablative conditioning.
• Persons of nonchildbearing potential or of childbearing potential with negative urine or serum pregnancy test on the day of first study injection.
• Persons of childbearing potential who have practiced adequate contraception or have abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose.
• Persons of childbearing potential who have agreed to continue adequate contraception or abstain from all activities that could result in pregnancy through 3 months after last study injection.
• Persons who are not currently breast/chestfeeding.
• Willingness to comply with study procedures and provide written informed consent.

Exclusion Criteria:

• History of a diagnosis or condition that, in the judgment of the Investigator, may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures.
• A documented positive human immunodeficiency virus (HIV) test.
• Treatment with alemtuzumab (Campath®), antithymocyte globulin (ATG), or any equivalent in-vivo T cell depleting agent within 12 months.
• HCT with ex-vivo T cell depletion.
• Low risk for CMV: HCT from related or unrelated donor with reduced intensity conditioning (RIC) and no other high-risk features.
• History of prior hematopoietic cell transplantation within 12 months.
• Receipt of prior investigational CMV vaccines or participation in another CMV therapeutic study that may interfere with study outcome measures as determined by the Investigator.
• Suspected or known allergic reaction to any component of any mRNA vaccine or its excipients.