BACKGROUND: Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.
OBJECTIVE: This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.
METHODS: Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.
RESULTS: The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.
LIMITATIONS: The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.
CONCLUSION: MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00316602.
Digital Object Identifier (DOI)
The study was funded by Bavarian Nordic through NIAID contract #N01-AI-40072 (http://www.niaid.nih.gov/Pages/default.aspx), and The National Institute of Allergy and Infectious Diseases (NIAID). These funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Bavarian Nordic provided grants to Rx Clinical Research, Inc. Rx Clinical Research, Inc. provided support in the form of salary for author DVD but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section. Bavarian Nordic provided support in the form of salaries for several authors (DB, AK, SR, GV, NA, TM, DS, RN, PY and PC), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
Greenberg R.N., Hurley M.Y., Dinh D.V., Mraz S., Vera J.G., von Bredow D., et al. (2015). Correction: A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis. PLOS ONE 10:11, e0142802. doi: http://dx.doi.org/10.1371/journal.pone.0142802
Greenberg, Richard N.; Hurley, Maria Yadira; Dinh, Dinh V.; Mraz, Serena; Vera, Javier Gomez; von Bredow, Dorothea; von Krempelhuber, Alfred; Roesch, Siegfried; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Meyer, Thomas Peter; Schmidt, Darja; Nichols, Richard; Young, Philip; and Chaplin, Paul, "A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis" (2015). Internal Medicine Faculty Publications. 84.
journal.pone.0138348.s002.TIF (904 kB)
S1 Fig. This is the Seroconversion ELISA PPS.
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S2 Fig. This is the Seroconversion PRNT PPS.
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S3 Fig. This is the GMT ELISA PPS.
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S4 Fig. This is the GMT PRNT PPS.
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S5 Fig. These are the figure legends for the supplemental figures.
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S1 IRB. These are the IRB approvals for the sites in Mexico.
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S2 IRB. These are the IRB listings.
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S3 IRB. This is the IRB approval for Dr. Greenberg’s site.
journal.pone.0138348.s010.DOCX (36 kB)
journal.pone.0138348.s011.PDF (657 kB)
journal.pone.0138348.s012.DOCX (14 kB)
S1 Table. These are adverse events tables.
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S2 Table. This shows the PRNT and ELISA Titers of Subjects not in PPS.