PMID- 25555381 OWN - NLM STAT- MEDLINE DCOM- 20150930 LR - 20220331 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 33 IP - 6 DP - 2015 Feb 4 TI - Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged >/=50 years: a randomised non-inferiority clinical trial. PG - 789-95 LID - S0264-410X(14)01667-3 [pii] LID - 10.1016/j.vaccine.2014.12.024 [doi] AB - Zostavax((R)) is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged >/=50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged >/=50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-gamma ELISPOT) assay and of the safety were secondary objectives. Participants were randomised to IM or SC administration (1:1). The baseline demographics were comparable between groups; mean age: 62.6 years (range: 50.0-90.5). The primary immunogenicity objectives were met (per protocol analysis): GMT ratio (IM/SC): 1.05 (95% CI: 0.93-1.18); GMFR: 2.7 (2.4-3.0). VZV immune response using IFN-gamma ELISPOT were comparable between groups. Frequencies of systemic adverse events were comparable between groups. Injection-site reactions were less frequent with IM than SC route: erythema (15.9% versus 52.5%), pain (25.6% versus 39.5%) and swelling (13.6% versus 37.3%), respectively. In adults aged >/=50 years, IM administration of Zostavax elicited similar immune responses to SC administration and was well tolerated, with fewer injection-site reactions than with SC administration. CI - Copyright (c) 2014 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Diez-Domingo, Javier AU - Diez-Domingo J AD - FISABIO-Public Health, Avda Cataluna 21, 46020 Valencia, Spain; Universidad Catolica de Valencia, 'San Vicente Martir', Valencia, Spain. Electronic address: diez_jav@gva.es. FAU - Weinke, Thomas AU - Weinke T AD - Klinikum Ernst von Bergmann, Charlottenstr. 72, 14467 Potsdam, Germany. Electronic address: tweinke@klinikumevb.de. FAU - Garcia de Lomas, Juan AU - Garcia de Lomas J AD - Department of Microbiology, University of Valencia, School of Medicine, Avda Blasco Ibanez 17, 46010 Valencia, Spain. Electronic address: jglomas@gmail.com. FAU - Meyer, Claudius U AU - Meyer CU AD - Pediatric Immunlogy, University Medical Center of the Johannes Gutenberg University, Ober Zahlbacher Str. 63, 55128 Mainz, Germany. Electronic address: meyer@uni-mainz.de. FAU - Bertrand, Isabelle AU - Bertrand I AD - Sanofi Pasteur MSD, 162 avenue Jean Jaures, CS 50712, 69367 Lyon Cedex 07, France. Electronic address: ibertrand@spmsd.com. FAU - Eymin, Cecile AU - Eymin C AD - Sanofi Pasteur MSD, 162 avenue Jean Jaures, CS 50712, 69367 Lyon Cedex 07, France. Electronic address: ceymin@spmsd.com. FAU - Thomas, Stephane AU - Thomas S AD - Sanofi Pasteur MSD, 162 avenue Jean Jaures, CS 50712, 69367 Lyon Cedex 07, France. Electronic address: sthomas@spmsd.com. FAU - Sadorge, Christine AU - Sadorge C AD - Sanofi Pasteur MSD, 162 avenue Jean Jaures, CS 50712, 69367 Lyon Cedex 07, France. Electronic address: csadorge@spmsd.com. LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20141230 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Viral) RN - 0 (Herpes Zoster Vaccine) RN - 0 (Vaccines, Attenuated) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Aged MH - Aged, 80 and over MH - Antibodies, Viral/*blood MH - Edema/etiology/physiopathology MH - Enzyme-Linked Immunospot Assay MH - Erythema/etiology/physiopathology MH - Female MH - Herpes Zoster/*blood/immunology/*prevention & control MH - Herpes Zoster Vaccine/*administration & dosage/adverse effects/immunology MH - Herpesvirus 3, Human/*immunology MH - Humans MH - Injections, Intramuscular MH - Injections, Subcutaneous MH - Interferon-gamma/blood MH - Male MH - Middle Aged MH - Pain/etiology/physiopathology MH - Vaccination MH - Vaccines, Attenuated OTO - NOTNLM OT - Herpes zoster OT - Intramuscular administration route OT - Randomised controlled trial OT - Shingles OT - Sub-cutaneous administration route OT - Varicella zoster virus vaccine EDAT- 2015/01/04 06:00 MHDA- 2015/10/01 06:00 CRDT- 2015/01/04 06:00 PHST- 2014/09/24 00:00 [received] PHST- 2014/12/10 00:00 [revised] PHST- 2014/12/11 00:00 [accepted] PHST- 2015/01/04 06:00 [entrez] PHST- 2015/01/04 06:00 [pubmed] PHST- 2015/10/01 06:00 [medline] AID - S0264-410X(14)01667-3 [pii] AID - 10.1016/j.vaccine.2014.12.024 [doi] PST - ppublish SO - Vaccine. 2015 Feb 4;33(6):789-95. doi: 10.1016/j.vaccine.2014.12.024. Epub 2014 Dec 30.