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A phase 1/2 study of an adjuvanted varicella-zoster virus subunit candidate vaccine in adult autologous hematopoietic stem-cell transplant recipients

Edward A. Stadtmauer, Keith M. Sullivan, Francisco M. Marty, Sanjeet S. Dadwal, Genovefa A. Papanicoleau, Thomas C. Shea, Sherif B. Mossad, Charalambos Andreadis, Jo-Anne H. Young, Francis K. Buadi, Mohamed El Idrissi, Thomas C. Heineman and Elchonon M. Berkowitz

Key points

  • HCT recipients have increased susceptibility to herpes zoster but live-attenuated vaccines are not appropriate for highly immunocompromised people.

  • An adjuvanted subunit vaccine against herpes zoster elicits strong immune response and acceptable safety profile in autologous HCT recipients.

Abstract

Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals.This was a phase 1/2, randomized, observer-blind, placebo-controlled study in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50–70 days earlier. Subjects (N=121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 µg VZV glycoprotein E (gE) adjuvanted with AS01B, three doses of gE adjuvanted with AS01E, one dose of saline followed by two doses of gE/AS01B, or three doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4+ T cells expressing ≥2 activation markers following induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to one year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01B 3-dose group than in the gE/AS01B 2-dose group but not higher than in the gE/AS01E 3-dose group. One serious adverse event (pneumonia) was considered vaccine-related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at Clinicaltrials.gov as #NCT00920218.

  • Submitted April 30, 2014.
  • Accepted September 1, 2014.