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Triplex is a viral vectored recombinant vaccine expressing three immunodominant CMV antigens. The vector is modified vaccinia Ankara (MVA), an attenuated, non\u2010replicating poxvirus derived from the vaccinia virus strain Ankara. It demonstrated tolerability and immunogenicity in healthy adults and HCT recipients, in whom it also reduced CMV reactivation. Here, we report feasibility, safety, and immunological outcomes of a pilot phase 1 trial (NCT03560752 at ClinicalTrials.gov) including 17 CMV\u2010seropositive recipients who received an HCT from a matched related donor (MRD) vaccinated with 5.1\u00a0\u00d7\u200910<jats:sup>8<\/jats:sup> pfu\/ml of Triplex before cell harvest (median 15, range 11\u201328\u2009days). Donor and recipient pairs who committed to participation in the trial resulted in exceptional adherence to the protocol. Triplex was well\u2010tolerated with limited adverse events in donors and recipients, who all engrafted with full donor chimerism. On day 28 post\u2010HCT, levels of functional vaccinia\u2010 and CMV\u2010specific CD137<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cells were significantly higher (<jats:italic>p<\/jats:italic>\u00a0&lt;\u2009.0001 and <jats:italic>p<\/jats:italic>\u00a0=\u2009.0174, respectively) in recipients of Triplex vaccinated MRD than unvaccinated MRD (control cohort). Predominantly, central and effector memory CMV\u2010specific T\u2010cell responses continued to steadily expand through 1\u2010year follow\u2010up. CMV viremia requiring antivirals developed in three recipients (18%). In summary, this novel approach represents a promising strategy applicable to different HCT settings for limiting the use of antiviral prophylaxis, which can impair and delay CMV\u2010specific immunity, leading to CMV reactivation requiring treatment.<\/jats:p>","DOI":"10.1002\/ajh.26824","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T07:36:03Z","timestamp":1672731363000},"page":"588-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus\u2010specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5258-5720","authenticated-orcid":false,"given":"Corinna","family":"La Rosa","sequence":"first","affiliation":[{"name":"Department of 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