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