One-Year Safety and Immunogenicity of Two Formulations of an Adjuvanted Varicella-Zoster VIRUS (VZV) Subunit Candidate Vaccine in Adult Autologous Hematopoietic CELL Transplant (HCT) Recipients

Introduction:The impaired B and T cell immunity of HCT recipients increases their susceptibility to infectious diseases like herpes zoster (HZ). However, the licensed live-attenuated HZ vaccine is not appropriate for highly immunocompromised individuals. Recombinant subunit vaccines are an alternative to live-attenuated vaccines. VZV glycoprotein E (gE) is an attractive candidate antigen. We report on the safety and immunogenicity of two formulations of a VZV subunit vaccine candidate administered on a 2- or 3-dose schedule to autologous HCT recipients.

Methods: This was a Phase I/II, randomized, placebo-controlled, multicenter study. Adults with multiple myeloma, non-Hodgkin B or T cell lymphoma, Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous HCT 50–70 days earlier were randomized 1:1:1:1 to receive 3 doses (at months 0, 1, and 3) of 50 mg gE combined with the adjuvant AS01_B (50 µg MPL/QS21) or AS01_E (25 µg MPL/QS21), 1 dose of saline followed by 2 doses of gE/AS01_B, or 3 doses of saline. Serum anti-gE antibody concentrations were measured by ELISA and frequencies of gE-specific CD4⁺T cells expressing ≥2 activation markers by intracellular cytokine staining up to month 15. Solicited local and systemic adverse events (AEs) were recorded up to 7 days after each immunization (graded 1–3). Unsolicited AEs were reported from the first immunization up to 30 days after the final immunization. Serious AEs were reported throughout the study. (Clinicaltrials.gov, NCT00920218).

Results: 120 subjects were vaccinated. gE-specific antibody concentrations and activated CD4⁺ T cell frequencies were higher with all gE/AS01 regimens than with saline at month 4 and persisted up to month 15 (all p<0.0001). For gE/AS01_B, 3 doses were more immunogenic than 2, but 3 doses of gE/AS01_B were not significantly more immunogenic than 3 doses of gE/AS01_E. The most common solicited AEs were pain, fatigue, and myalgia. Overall, grade 3 AEs were reported in 10.3%–36.7% of vaccine and ≤6.7% of saline recipients. One non-fatal SAE was considered possibly related to vaccination in the gE/AS01_B 2-dose group. Eleven subjects died, of which seven died from malignancy recurrence. Four cases of HZ were confirmed during the study, two each in the gE/AS01_E3-dose and saline groups.

Conclusions: Both gE/AS01_B and gE/AS01_E formulations and both schedules were immunogenic and well tolerated in autologous HCT recipients.