title: Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial.
abstract: BACKGROUND
  GSK's varicella vaccine contains human serum albumin (HSA) which is used to stabilize the virus and prevent immunogens from adhering to the injection vial walls. However, because HSA is derived from human blood, there is a theoretical risk that it might contain infectious agents which could be unsafe for humans. Given this concern, a study was undertaken to compare the immunogenicity and safety of a new formulation without HSA with the currently licensed varicella vaccine in the Czech Republic and Hungary.
  
  
  METHODS
  Healthy children aged 11-21 months received two doses of the varicella vaccine either with or without HSA. Antibody titres against varicella-zoster virus (anti-VZV) were measured 42 days after each dose, using an immunofluorescence assay (IFA, cut-off = 4dilution(-1)) and enzyme linked immunosorbent assay (ELISA, cut-off = 25 mIU/ml). Solicited local symptoms were recorded during a 4-day post-vaccination follow-up period; solicited general and unsolicited symptoms were recorded during a 43-day post-vaccination follow-up period and serious adverse event (SAEs) were recorded throughout the study.
  
  
  RESULTS
  Of 244 children (mean age = 15.2 months [SD = 3.2]) vaccinated in the study, 233 (vaccine without HSA N = 117; vaccine containing HSA N = 116) formed the according-to-protocol immunogenicity cohort. Observed seroconversion/seroresponse rates were >98 and 100 %, 42 days after doses 1 and 2, respectively. The rates were within the same range in both groups, irrespective of the testing assay. The varicella vaccine without HSA was non-inferior to the licensed vaccine in terms of anti-VZV antibody Geometric Mean Titre/Concentration ratio (1.12 [95 % CI:0.86-1.46] by IFA; 1.12 [95 % CI:0.93-1.33] by ELISA) approximately six weeks after the first dose of the 2-dose vaccination course. The incidence of solicited and unsolicited symptoms was similar after both vaccines; low-grade fever was numerically higher after the first dose of the varicella vaccine without HSA. Seven SAEs were reported, none of which were fatal or considered to be vaccine-related.
  
  
  CONCLUSIONS
  The first dose of a new varicella vaccine without HSA was immunologically non-inferior to the licensed varicella vaccine. After two doses, both vaccines had acceptable safety profiles in children aged 11-21 months in the Czech Republic and Hungary.
  
  
  BACKGROUND
  NCT00568334 , registered on 5 December 2007 ( www.clinicaltrials.gov ).
authors.affiliation: Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 50001, Hradec Kralove, Czech Republic. prymula@seznam.cz.
authors.forename: Roman
authors.initials: R
authors.lastname: Prymula
authors.affiliation: Primary Care Paediatric Praxis, No 8, Miskolc, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Simko
authors.affiliation: GSK Vaccines, Avenue Fleming 20 B-1300, Wavre, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Povey
authors.affiliation: Szent László Hospital, Gyali Street 5-7, Budapest, 1097, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kulcsar
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D019433:Chickenpox Vaccine / Q000009:adverse effects / Q000276:immunology*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D012709:Serum Albumin
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D019433:Chickenpox Vaccine; D012709:Serum Albumin