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: Richard N Greenberg, Edgar Turner Overton, David W Haas, Ian Frank, Mitchell Goldman, Alfred von Krempelhuber, Garth Virgin, Nicole Bädeker, Jens Vollmar, Paul Chaplin
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 5 Pg. 749-58 (Mar 01 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 23225902 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Viral
• Biomarkers
• Smallpox Vaccine

Topics

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