# Transfer of vaccine-induced immunity from immunocompetent stem cell donor as antiviral immunotherapy to protect high-risk transplant recipients from cytomegalovirus reactivation

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2023 · $688,080

## Abstract

PROJECT SUMMARY/ABSTRACT
Preemptive use of antivirals (PET) to control cytomegalovirus (CMV) viremia in hematopoietic cell transplant
recipients (HCT-R) was a therapeutic advance balanced by elevated toxicity. Newer drugs such as letermovir
(Prevymis) have lower toxicity with increased efficacy. FDA approval of Prevymis was for 100 consecutive days
(d) of prophylaxis which reduced CMV reactivation by ~2fold in high and low risk HCT-R. The antiviral effect
waned after 18 weeks without a survival benefit. We co-developed with NCI, a modified vaccinia Ankara (MVA)
vaccine named Triplex expressing CMV immunodominant antigens. We published a safety study in healthy
volunteers showing strong immunogenicity of the vaccine (NCT1941056), which preceded a published
successful placebo-controlled and randomized Phase 2 trial (NCT2506933) of CMV-positive (P) HCT-R with
either CMV-Positive (CMV-P) or CMV-Negative (CMV-N) HCT donors (HCT-D). The Phase 2 trial met its primary
endpoint of reduced CMV reactivation in the vaccine arm by 50% with accelerated reconstitution of protective
CMV immunity. Triplex outcomes can be improved; one approach is to vaccinate the immunocompetent HCT-D
as demonstrated by our impressive preliminary results from an ongoing pilot study (NCT3560752) which showed
that all HCT-R (N=12) receiving stem cells from vaccinated matched related donors (MRD) were protected from
requiring PET. We hypothesize that Triplex injection of HCT-D will initiate protective immunity by transfer of
expanded CMV-protective T cells as a component of the stem cell infusion to the HCT-R, preceding dosing with
Prevymis, thereby eliminating its need. In Aim 1, we propose a Phase 2 randomized placebo-control trial (in
centers not prescribing Prevymis for MRD-HCT) with eligibility of CMV-P HCT-R with MRD (intermediate risk)
undergoing T-cell replete HCT for hematologic malignancy. CMV-P HCT-R will be randomized to receive stem
cells from HCT-D receiving a single injection of Triplex or placebo identical to the pilot trial. This trial will show
that a single HCT-D vaccination is sufficient to replace 100d of Prevymis to prevent PET usage in MRD-HCT-R.
In the 180d trial period we will assess PET usage, measure CMV-specific CD8/CD4 T cells with the goal of
associating frequency, memory phenotype, and gene expression with protection against reactivation leading to
viremia or disease. To extend Triplex benefit to haploidentical HCT-R treated with post-HCT cyclophosphamide
(PTCY) who are at high risk for CMV reactivation, in Aim 2 we propose a two-stage (Phase 1b/2) trial to choose
an optimal Triplex vaccine strategy that promotes effective immune reconstitution with minimal CMV reactivation.
All HCT-D will be vaccinated once with Triplex, and all HCT-R will be boosted with 3 Triplex injections on d28,
56, and 100. The initial open-label Phase 1b segment will either have patients abstain from Prevymis, or given
21d-100d of prophylaxis. The vaccination regimen with the l...

## Key facts

- **NIH application ID:** 10659635
- **Project number:** 1R01CA266783-01A1
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Don J Diamond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $688,080
- **Award type:** 1
- **Project period:** 2023-05-02 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10659635

## Citation

> US National Institutes of Health, RePORTER application 10659635, Transfer of vaccine-induced immunity from immunocompetent stem cell donor as antiviral immunotherapy to protect high-risk transplant recipients from cytomegalovirus reactivation (1R01CA266783-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10659635. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*