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

• Published in: The Journal of infectious diseases Vol. 207; no. 5; pp. 749 - 758
• Main Authors: Greenberg, Richard N., Overton, Edgar Turner, Haas, David W., Frank, Ian, Goldman, Mitchell, von Krempelhuber, Alfred, Virgin, Garth, Bädeker, Nicole, Vollmar, Jens, Chaplin, Paul
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2013
• Subjects: Adolescent; Adult; Antibodies; Antibodies, Viral - blood; Applied microbiology; Biological and medical sciences; Biomarkers; Disease risks; Drug-Related Side Effects and Adverse Reactions - epidemiology; Enzyme linked immunosorbent assay; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV Infections - complications; HIV Infections - immunology; Human immunodeficiency virus; Human viral diseases; Humans; Immune response; Immunologic Memory; Infectious diseases; Major and Brief Reports; MAJOR ARTICLES AND BRIEF REPORTS; Male; Medical sciences; Microbiology; Middle Aged; Smallpox; Smallpox - immunology; Smallpox - prevention & control; Smallpox Vaccine - administration & dosage; Smallpox Vaccine - adverse effects; Smallpox Vaccine - immunology; Smallpox vaccines; T lymphocytes; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccinia; Vaccinia virus - immunology; Variola; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Young Adult; Infection; Immunopathology; Smallpox; Skin disease; Immunogenicity; Efficiency; Viral disease; AIDS; Vaccine; Immune deficiency; Vaccinia
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis753

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. Clinical Trials Registration. NCT00189904.