title: Effect of vaccination with modified vaccinia Ankara (ACAM3000) on subsequent challenge with Dryvax.
abstract: BACKGROUND
  Despite the success of smallpox vaccination, the immunological correlates of protection are not fully understood. To investigate this question, we examined the effect of immunization with modified vaccinia Ankara (MVA) on subsequent challenge with replication-competent vaccinia virus (Dryvax).
  
  
  METHODS
  Dryvax challenge by scarification was conducted in 36 healthy subjects who had received MVA (n = 29) or placebo (n = 7) in a previous study of doses and routes of immunization. Subjects were followed up for clinical take, viral shedding, and immune responses.
  
  
  RESULTS
  MVA administration attenuated clinical takes in 21 (72%) of 29 subjects, compared with 0 of 7 placebo recipients (P = .001). Attenuation was most significant in MVA groups that received 1 x 10(7) median tissue culture infective doses (TCID(50)) intradermally (P = .001) and 1 x 10(7) TCID(50) intramuscularly (P = .001). Both duration and peak titer of viral shedding were reduced in MVA recipients. Peak neutralizing antibody responses to vaccinia virus or MVA previously induced by MVA immunization were associated with attenuated takes (P = .02) and reduced duration (P = .001) and titer (P = .005) of viral shedding.
  
  
  CONCLUSIONS
  MVA immunization results in clinical and virologic protection against Dryvax challenge. Protection is associated with prior induction of neutralizing antibodies to MVA or vaccinia virus. MVA administered intradermally has protective and immunologic responses similar to those of a 10-fold-higher dose given subcutaneously.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Marissa B
authors.initials: MB
authors.lastname: Wilck
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: Lizanne C
authors.initials: LC
authors.lastname: Noble
authors.forename: Jane A
authors.initials: JA
authors.lastname: Kleinjan
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: D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D012900:Smallpox Vaccine / Q000276:immunology / Q000494:pharmacology*; D013997:Time Factors; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology / Q000494:pharmacology; D014616:Vaccinia virus / Q000276:immunology*; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C078786:DryVax vaccine; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated