*Purpose: Cytomegalovirus (CMV) is a significant pathogen in pregnancy and immunocompromised patients. Antiviral prophylaxis is limited by toxicities, recurrent infection, and resistance. A safe and protective CMV vaccine is highly desirable.

*Methods: HB-101, a CMV vaccine, consists of non-replicating lymphocytic choriomeningitis virus vectors, expressing either the CMV tegument protein pp65 or a truncated isoform of the fusion protein gB. The safety and immunogenicity of HB-101 were evaluated in a randomized, placebo-controlled, double-blind phase I trial (NCT02798692). Three cohorts (1: 2.6×10⁶; 2: 2.6×10⁷and 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. Humoral and cellular responses against gB and the LCMV vector and cellular responses against pp65 were measured.

*Results: Injection site pain was the most frequent solicited adverse event (SAE)(Figure 1). Among the general SAE, malaise, fatigue and myalgia were most frequently reported. HB-101 induced gB-specific dose-dependent IgG antibody responses (Figure 2). All doses induced neutralizing antibodies and a robust, boosterable, durable T-cell response by IFNγ ELISPOT against CMV gB and pp65. Polychromatic flow cytometry indicated induction of a high proportion of polyfunctional HCMV-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.

*Conclusions: A novel CMV vaccine with a good safety profile in healthy volunteers, HB-101 elicits strong humoral and cellular immune responses. We are enrolling a phase 2 trial in living donor kidney transplant recipients at high risk for CMV infection, with 2-3 doses of vaccine given prior to transplant (Figure 3) (NCT03629080).

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