title: Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled trial.
abstract: BACKGROUND
  Modified vaccinia Ankara (MVA-BN, IMVAMUNE) is emerging as a primary immunogen and as a delivery system to treat or prevent a wide range of diseases. Defining the safety and immunogenicity of MVA-BN in key populations is therefore important.
  
  
  METHODS
  We performed a dose-escalation study of MVA-BN administered subcutaneously in 2 doses, one on day 0 and another on day 28. Twenty-four hematopoietic stem cell transplant recipients were enrolled sequentially into the study, and vaccine or placebo was administered under a randomized, double-blind allocation. Ten subjects received vaccine containing 10(7) median tissue culture infective doses (TCID50) of MVA-BN, 10 subjects received vaccine containing 10(8) TCID50 of MVA-BN, and 4 subjects received placebo.
  
  
  RESULTS
  MVA-BN was generally well tolerated at both doses. No vaccine-related serious adverse events were identified. Transient local reactogenicity was more frequently seen at the higher dose. Neutralizing antibodies (NAb) to Vaccinia virus (VACV) were elicited by both doses of MVA-BN and were greater for the higher dose. Median peak anti-VACV NAb titers were 1:49 in the lower-dose group and 1:118 in the higher-dose group. T-cell immune responses to VACV were detected by an interferon γ enzyme-linked immunosorbent spot assay and were higher in the higher-dose group.
  
  
  CONCLUSIONS
  MVA-BN is safe, well tolerated, and immunogenic in HSCT recipients. These data support the use of 10(8) TCID50 of MVA-BN in this population.
  
  
  BACKGROUND
  NCT00565929.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA. srwalsh@bidmc.harvard.edu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Walsh
authors.forename: Marissa B
authors.initials: MB
authors.lastname: Wilck
authors.forename: David J
authors.initials: DJ
authors.lastname: Dominguez
authors.forename: Elise
authors.initials: E
authors.lastname: Zablowsky
authors.forename: Shringkhala
authors.initials: S
authors.lastname: Bajimaya
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Gagne
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Verrill
authors.forename: Jane A
authors.initials: JA
authors.lastname: Kleinjan
authors.forename: Alka
authors.initials: A
authors.lastname: Patel
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Heather
authors.initials: H
authors.lastname: Hill
authors.forename: Aruna
authors.initials: A
authors.lastname: Acharyya
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D011994:Recombinant Proteins; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; C527606:smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
keywords: clinical trial; dose; immunogenicity; modified vaccinia ankara; safety; stem cell transplant