title: Safety and immunogenicity of modified vaccinia Ankara (ACAM3000): effect of dose and route of administration.
abstract: BACKGROUND
  We conducted a clinical trial of the safety and immunogenicity of modified vaccinia Ankara (MVA) to examine the effects of dose and route of administration.
  
  
  METHODS
  Seventy-two healthy, vaccinia virus-naive subjects received 1 of 6 regimens of MVA (ACAM3000) or placebo consisting of 2 administrations given 1 month apart.
  
  
  RESULTS
  MVA was generally well tolerated at all dose levels and by all routes. More pronounced local reactogenicity was seen with the intradermal and subcutaneous routes than with intramuscular administration. Binding antibodies to whole virus and neutralizing antibodies to the intracellular mature virion and extracellular enveloped virion forms of vaccinia virus were elicited by all routes of MVA administration and were greater for the higher dose by each route. Similar levels of neutralizing antibodies were seen at a 10-fold-lower dose given intradermally (1 x 10(7) median tissue culture infective doses [TCID(50)]), compared with responses after 1 x 10(8) TCID(50) given intramuscularly or subcutaneously. T cell immune responses to vaccinia virus were detected by an interferon gamma enzyme-linked immunospot assay but had no clear relationship to dose or route.
  
  
  CONCLUSIONS
  These data suggest that intradermal immunization with MVA provides a dose-sparing effect by eliciting antibody responses similar in magnitude and kinetics to those elicited by the intramuscular or subcutaneous routes but at a 10-fold-lower dose.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Marissa B
authors.initials: MB
authors.lastname: Wilck
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Walsh
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Grandpre
authors.forename: Colleen
authors.initials: C
authors.lastname: Devoy
authors.forename: Ayush
authors.initials: A
authors.lastname: Giri
authors.forename: Jane A
authors.initials: JA
authors.lastname: Kleinjan
authors.forename: Lizanne C
authors.initials: LC
authors.lastname: Noble
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Stevenson
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects; D014616:Vaccinia virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated