Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia Ankara as a smallpox vaccine in HIV-infected subjects

J Infect Dis. 2013 Mar 1;207(5):749-58. doi: 10.1093/infdis/jis753. Epub 2012 Dec 7.

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.

Trial registration: ClinicalTrials.gov NCT00189904.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Biomarkers*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • HIV Infections / complications*
  • HIV Infections / immunology
  • Humans
  • Immunologic Memory
  • Male
  • Middle Aged
  • Smallpox / immunology
  • Smallpox / prevention & control*
  • Smallpox Vaccine / administration & dosage
  • Smallpox Vaccine / adverse effects*
  • Smallpox Vaccine / immunology*
  • Vaccinia virus / immunology*
  • Young Adult

Substances

  • Antibodies, Viral
  • Biomarkers
  • Smallpox Vaccine

Associated data

  • ClinicalTrials.gov/NCT00189904