Introduction: ASP0113 is a first-in-class, DNA-based vaccine in development for the prevention of CMV infection in at-risk hematopoietic cell transplant.

Methods: A Phase 1, single-blind, parallel-group, PK and immunogenicity study was conducted in 15 CMV-seropositive healthy subjects (H+), 15 CMV-seronegative healthy subjects (H–), and 14 CMV-seronegative matched dialysis subjects (D–). ASP0113 (5 mg) was administered intramuscularly on Weeks 1, 5, 9, and 25. Blood samples were serially collected to assess immune response up to 27 weeks. B-cell response was assessed by measurement of anti-glycoprotein B (gB) antibodies by ELISA. T-cell response to phosphoprotein 65 was assessed in isolated PBMCs using ELISPOT (1-day assay, to measure effector memory T-cells), cultured ELISPOT (10-day assay, to measure memory T-cells), and in blood using the QuantiFERON-CMV assay. Safety was also monitored throughout the study.

Results: ASP0113 was well tolerated. Across all study groups, injection site pain was the most common TEAE, all were Grade 2 or less; there were no deaths or SAEs. Plasma plasmid concentrations showed dual peaks at 2–10 h and 24–48 h after administration. Plasmid concentrations rapidly declined (approx. 7 h half-life) and reached the lower limit of detection (100 copies/mL) 7 days after administration. Anti-gB antibody response were not detected in any seronegative subjects. In the 1-day ELISPOT, T-cell response rates were 36% (11–69%) in H– and 0% in D– subjects. Response rates of 67% (95% CI: 35–90%) and 33% (95% CI: 10–65%) in H– and D– subjects, respectively, were demonstrated by cultured ELISPOT. The response rate appeared to increase over time in both groups with highest responses achieved at Week 27. The magnitude of response in D– subjects was less than in H– subjects. The response rate in H– and D– subjects using the QuantiFERON assay was 25% (95% CI: 6–57%). The QuantiFERON assay demonstrated less sensitivity, but had high concordance with the cultured ELISPOT assay.

Conclusions: ASP0113 was well tolerated. B-cell responses were undetectable, while T cell responses were demonstrated in both H- and D- subjects.

CITATION INFORMATION: Bonate P, Van Sant C, Cho K, Zook E, Smith L, Boutsaboualoy S, Wang X, Wu R, Koester A, Rammelsberg D, Goldwater R, Marbury T. ASP0113 Elicits an Immune Response in CMV-Seronegative Dialysis Patients: Comparison to Healthy Subjects. Am J Transplant. 2017;17 (suppl 3).

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