Methods: HB-101 is a CMV vaccine consisting of two non-replicating lymphocytic choriomeningitis virus vectors, one expressing the human CMV antigen pp65 and the other a truncated, more antigenic isoform of the CMV fusion protein gB. The safety and immunogenicity of HB-101 were evaluated in a randomized, placebo-controlled, double-blind phase I dose-escalating trial (NCT02798692). Three dosing cohorts (1: 2.6x106; 2: 2.6x107and 3: 2.6 x 108FFU)of 18 subjects each were enrolled. On day 0, month 1, and month 3, HB-101 or placebo was administered to 14 and 4 subjects, respectively. Immunogenicity studies included cellular responses against pp65, and humoral and cellular responses against gB and the LCMV vector.
Results: Injection site pain was the most frequently reported solicited adverse event (SAE). It affected 57.1% of HB-101 recipients in both cohorts 1 and 2 and 92.9% in cohort 3. Among the general SAE malaise, fatigue and generalized myalgia were most frequently reported. All SAE were generally mild to moderate and lasted less than 8 days. No serious adverse events and no abnormal lab tests were noted during the active phase of the study. HB-101 induced gB-specific IgG antibody responses at all doses, in a dose-dependent manner. All three dose levels also induced antibodies that neutralized HCMV infection in cultured human fibroblasts (MRC-5 cells), and resulted in a robust, boosterable and durable T-cell response by IFNγ ELISPOT for CMV gB and pp65. Polychromatic flow cytometry indicated induction of a high proportion of polyfunctional CMV-specific CD8 and CD4 T-cells. CD8 T-cells expressing IFNγ, IL2 and TNFα without CD107a were among the most prominent populations induced against CMV pp65.
Conclusion: HB-101 is a novel CMV vaccine with a good safety profile in healthy volunteers, eliciting strong humoral and cellular immune responses. We are starting a phase 2 trial in kidney transplant candidates at higher risk for CMV infection. We plan to give multiple vaccinations prior to living donor kidney transplant, and will follow post transplant for safety, immunogenicity, and efficacy.
C. N. Kotton,
G. Thiry, Hookipa: Consultant , Consulting fee .
B. DeVos, Hookipa: Consultant , Consulting fee .
F. De Boever, Hookipa: Consultant , Consulting fee .
G. Leroux-Roels, Hookipa: Consultant , Consulting fee .
A. Lilja, Hookipa: Employee , Salary .
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