Safety, Immunogenicity, and Surrogate Markers of Clinical Efficacy for Modified Vaccinia Ankara as a Smallpox Vaccine in HIV-Infected Subjects

University of Kentucky School of Medicine, Infectious Diseases Division, Lexington, Kentucky.
The Journal of Infectious Diseases (Impact Factor: 5.78). 12/2012; 207(5). DOI: 10.1093/infdis/jis753
Source: PubMed

ABSTRACT Background. 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 MVA was assessed in 91 HIV-infected adult subjects (CD4 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 uninfected subjects.Results. MVA was well tolerated and immunogenic in all subjects. Antibody responses were comparable between uninfected and HIV infected populations with only one significantly lower total antibody titer at 2 weeks post 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.Clinical Trial Registration. NCT00189904.

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