A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects

• DOI: 10.1371/journal.pone.0157335
• Publication Date: 2016-06-22T22:54:42Z
• Authors: Richard N. Greenberg; Christine M. Hay; Jack T. Stapleton; Thomas C. Marbury; Eva Wagner; Eva Kreitmeir; Siegfried Röesch; Alfred von Krempe...; Philip Young; Richard Nichols; Thomas P. Meyer; Darja Schmidt; Josef Weigl; Garth Virgin; Nathaly Arndtz-Wi...; Paul Chaplin
• Keywords: Modified vaccinia Ankara; Seroconversion; Smallpox vaccine; myalgia

Background Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of (MVA) was assessed in 56–80 years old population. Methods MVA with virus titer 1 x 108 TCID50/dose administered via subcutaneous injection to year vaccinia-experienced subjects (N = 120). Subjects received either two injections (MM group) or one Placebo (PM four weeks apart. Safety evaluated by assessment adverse events (AE), focused physical exams, electrocardiogram recordings laboratories. Solicited AEs consisted set pre-defined expected local reactions (erythema, swelling, pain, pruritus, induration) systemic symptoms (body temperature, headache, myalgia, nausea fatigue) were recorded on memory aid for an 8-day period following each injection. The terms humoral immune responses measured vaccinia-specific enzyme-linked immunosorbent assay (ELISA) plaque reduction neutralization test (PRNT) before at different time points after vaccination. Results Vaccinations well tolerated all subjects. No serious event related no case myopericarditis reported. overall incidence unsolicited similar both groups. For groups final vaccination (i.e. Visit 4) follows: Seroconversion (SC) rates (doubling titers from baseline) specific antibody ELISA 83.3% Group MM 82.8% PM (difference 0.6% 95% exact CI [-13.8%, 15.0%]), 90.0% 77.6% PRNT 12.4% [-1.1%, 27.0%]). Geometric mean (GMT) 804.1 605.8 (with ratio GMTs 1.33 [0.96, 1.84]). Similarly, 210.3 126.7 1.66 [0.95, 2.90]). Conclusions One doses safe immunogenic cases observed vaccinations MVA. safety, reactogenicity that seen younger (18–55 old) healthy populations investigated other trials. results suggest single dose population sufficient rapidly boost long-term B cell response induced prior traditional Trial Registration ClinicalTrials.gov NCT00857493