title: Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia Ankara as a smallpox vaccine in HIV-infected subjects.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-infected persons are at higher risk for serious complications associated with traditional smallpox vaccines. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need.
  
  
  METHODS
  The safety and immunogenicity of modified vaccinia Ankara (MVA) was assessed in 91 HIV-infected adult subjects (CD4(+) T-cell counts, ≥350 cells/mm(3)) and 60 uninfected volunteers. The primary objectives were to evaluate the safety of MVA and immunogenicity in HIV-infected and uninfected subjects. As a measure of the potential efficacy of MVA, the ability to boost the memory response in people previously vaccinated against smallpox was evaluated by the inclusion of vaccinia-experienced HIV-infected and HIV-uninfected subjects.
  
  
  RESULTS
  MVA was well tolerated and immunogenic in all subjects. Antibody responses were comparable between uninfected and HIV-infected populations, with only 1 significantly lower total antibody titer at 2 weeks after the second vaccination, while no significant differences were observed for neutralizing antibodies. MVA rapidly boosted the antibody responses in vaccinia-experienced subjects, supporting the efficacy of MVA against variola.
  
  
  CONCLUSIONS
  MVA is a promising candidate as a safer smallpox vaccine, even for immunocompromised individuals, a group for whom current smallpox vaccines have an unacceptable safety profile.
authors.affiliation: Infectious Diseases Division, University of Kentucky School of Medicine, Lexington, KY 40536-0093, USA. rngree01@uky.edu
authors.forename: Richard N
authors.initials: RN
authors.lastname: Greenberg
authors.forename: Edgar Turner
authors.initials: ET
authors.lastname: Overton
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.forename: Mitchell
authors.initials: M
authors.lastname: Goldman
authors.forename: Alfred
authors.initials: A
authors.lastname: von Krempelhuber
authors.forename: Garth
authors.initials: G
authors.lastname: Virgin
authors.forename: Nicole
authors.initials: N
authors.lastname: Bädeker
authors.forename: Jens
authors.initials: J
authors.lastname: Vollmar
authors.forename: Paul
authors.initials: P
authors.lastname: Chaplin
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D015415:Biomarkers; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D012899:Smallpox / Q000276:immunology / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D012900:Smallpox Vaccine