Long-term Immunogenicity and Safety of an Investigational Herpes Zoster Subunit Vaccine in Older Adults
Background: An investigational subunit vaccine containing varicella-zoster virus glycoprotein E (gE) and the AS01B Adjuvant System is being evaluated for the prevention of herpes zoster (HZ) in older adults. A phase II clinical trial evaluating different formulations of the candidate vaccine (containing 25 µg, 50 µg, or 100 µg gE; adjuvanted with AS01B) was conducted in adults ≥60 years of age, and showed that all 2-dose adjuvanted vaccine formulations elicited robust cellular and humoral immune responses in older adults, for up to 3 years post-vaccination.1 The 50 µg gE formulation (HZ/su) was selected for further clinical development. In order to gain insight into the potential of this investigational vaccine to provide long-term protection against HZ, we assessed the persistence of the vaccine-induced immune responses for up to 6 years post-vaccination in subjects who received 2-doses of HZ/su.
Methods: This phase II, open-label, multicenter, single group trial conducted in the Czech Republic, Germany, Sweden and the Netherlands (NCT01295320) followed 129 subjects who had received 2 doses (2 months [M] apart) of HZ/su (50 µg gE + AS01B) during the previous trial (NCT00434577). Vaccine-induced immune responses (frequencies of antigen-specific CD4+ T cells expressing ≥2 activation markers measured by intracellular cytokine staining after in vitro stimulation with gE and serum anti-gE antibody concentrations measured by ELISA) from these subjects were evaluated at 48, 60 and 72 M after the first HZ/su dose. Serious adverse events (SAEs) were recorded from M48 to M72.
Results: Participant flow is shown in Figure 1. 6 years after the 2-dose vaccination with HZ/su, gE-specific cell-mediated immune (CMI) responses and anti-gE antibody concentrations had decreased, but remained higher than pre-vaccination values (Figure 2). M72 gE-specific CMI response median values were 3.8 times higher than pre-vaccination values. No vaccine-related SAEs were reported from M48 to M72.
Conclusion: Persistence of immune response was observed for up to 6 years after 2-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.
1 R. Chlibek et al. Vaccine32(2014):1745–1753.
GlaxoSmithKline Vaccines: Employee and Shareholder, Salary
L. Rombo, GSK: Investigator, Research support
K. Pauksens, None
T. F. Schwarz, GlaxoSmithKline: Board Member, Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium
G. Plassmann, GSK: Investigator, Investigator duty
J. H. Richardus, Glaxo Smith Kline: Grant Investigator, Grant recipient
G. G. C. Van Rijckevorsel, None
G. Catteau, GSK: Employee, Salary
T. Heineman, GSK Vaccines: Employee and Shareholder, Salary