Roman Chlibek1, Jan Smetana2, Karlis Pauksens3, Lars Rombo4, J Anneke R Van den Hoek5, Jan H Richardus6, Georg Plassmann7, Tino F Schwarz8, Edouard Ledent9, Thomas C Heineman10. 1. Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. 2. Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. Electronic address: smetana@pmfhk.cz. 3. Department of Medical Science, Section of Infectious Diseases, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden. 4. Clinical Research Center, Sormland County Council, Eskilstuna, Sweden; Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. 5. Public Health Service Amsterdam, The Netherlands; Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, Amsterdam, The Netherlands. 6. Municipal Public Health Service Rotterdam-Rijnmond, Rotterdam, The Netherlands. 7. Unterfrintroper Hausarztzentrum, Essen, Germany. 8. Central Laboratory and Vaccination Centre, Stiftung Juliusspital, Würzburg, Germany. 9. GlaxoSmithKline Vaccines, Wavre, Belgium. 10. GlaxoSmithKline Vaccines, King of Prussia, PA, USA.
Abstract
BACKGROUND: This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant systemAS01B. METHODS: In this phase II, single-blind, randomized, controlled study, adults aged ≥60years (N=714) received one dose of 100μggE/AS01B, two doses, two months apart, of 25, 50, or 100μggE/AS01B, or two doses of unadjuvanted 100μggE/saline. Frequencies of CD4(+) T cells expressing ≥2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA. RESULTS: Frequencies of gE-specific CD4(+) T cells were >3-fold higher after two doses of all gE/AS01B formulations than after one dose of 100μggE/AS01B or two doses of 100μggE/saline. Frequencies were comparable after two doses of 25, 50, or 100μggE/AS01B. Serumanti-gE antibody concentrations were comparable after two doses of 50 or 100μggE/AS01B and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01B formulations were similar but greater than with gE/saline. CONCLUSIONS: The three formulations of gE/AS01B were immunogenic and well tolerated in adults aged ≥60years. Two vaccinations with gE/AS01B induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).
RCT Entities:
BACKGROUND: This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system AS01B. METHODS: In this phase II, single-blind, randomized, controlled study, adults aged ≥60years (N=714) received one dose of 100μggE/AS01B, two doses, two months apart, of 25, 50, or 100μggE/AS01B, or two doses of unadjuvanted 100μggE/saline. Frequencies of CD4(+) T cells expressing ≥2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA. RESULTS: Frequencies of gE-specific CD4(+) T cells were >3-fold higher after two doses of all gE/AS01B formulations than after one dose of 100μggE/AS01B or two doses of 100μggE/saline. Frequencies were comparable after two doses of 25, 50, or 100μggE/AS01B. Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100μggE/AS01B and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01B formulations were similar but greater than with gE/saline. CONCLUSIONS: The three formulations of gE/AS01B were immunogenic and well tolerated in adults aged ≥60years. Two vaccinations with gE/AS01B induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).
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