Journal Article

Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: A phase II, randomized, controlled study

Plassmann, Georg, Schwarz, Tino F., Heineman, Thomas C., Chlibek, Roman, Van den Hoek, J. Anneke R., Rombo, Lars, Richardus, Jan H., Ledent, Edouard, Pauksens, Karlis, Smetana, Jan

2014

Overview

•We investigated a herpes zoster vaccine candidate at different antigen doses, and with or without the AS01B Adjuvant System.•All adjuvanted vaccine formulations were immunogenic and well-tolerated in adults ≥60 years of age.•Two vaccinations with the adjuvanted vaccine candidate induced a greater immune response than one.•The dose of varicella-zoster virus glycoprotein E impacted humoral but not cellular immune responses. 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. 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. 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. 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).

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Adjuvant / adjuvants / Adjuvants, Immunologic - administration & dosage / Age / Aged / Allergy and Immunology / antibodies / Antibodies, Viral - blood / Applied microbiology / Biological and medical sciences / blood serum / CD4-positive T-lymphocytes / CD4-Positive T-Lymphocytes - immunology / cell-mediated immunity / cytokines / Dose-Response Relationship, Immunologic / elderly / Female / Fundamental and applied biological sciences. Psychology / glycoproteins / Herpes zoster / Herpes Zoster Vaccine - adverse effects / Herpes Zoster Vaccine - immunology / Herpes Zoster Vaccine - therapeutic use / Human alphaherpesvirus 3 / Human viral diseases / Humans / immune response / Immunity, Cellular / Immunity, Humoral / Immunization Schedule / Immunogenicity / Infectious diseases / Male / Medical sciences / Microbiology / Middle Aged / Miscellaneous / Older people / Pain / Single-Blind Method / staining / vaccination / Vaccine / Vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / Vaccines, Subunit - adverse effects / Vaccines, Subunit - immunology / Vaccines, Subunit - therapeutic use / Varicella-zoster virus / Viral diseases / Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye / Virology