INTRODUCTION: To guide the use of modified vaccinia Ankara (MVA) vaccine in 
response to a release of smallpox virus, the immunogenicity and safety of 
shorter vaccination intervals, and administration by jet injector (JI), were 
compared to the standard schedule of administration on Days 1 and 29 by syringe 
and needle (S&N).
METHODS: Healthy adults 18-40years of age were randomly assigned to receive MVA 
vaccine subcutaneously by S&N on Days 1 and 29 (standard), Days 1 and 15, or 
Days 1 and 22, or to receive the vaccine subcutaneously by JI on Days 1 and 29. 
Blood was collected at four time points after the second vaccination for plaque 
reduction neutralization test (PRNT) (primary endpoint) and ELISA (secondary 
endpoint) antibody assays. For each subject, the peak PRNT (or ELISA) titer was 
defined by the highest PRNT (or ELISA) titer among all available measurements 
post second vaccination. Non-inferiority of a non-standard arm compared to the 
standard arm was met if the upper limit of the 98.33% confidence interval of the 
difference in the mean log2 peak titers between the standard and non-standard 
arm was less than 1.
RESULTS: Non-inferiority of the PRNT antibody response was not established for 
any of the three non-standard study arms. Non-inferiority of the ELISA antibody 
response was established for the Day 1 and 22 compressed schedule and for 
administration by JI. Solicited local reactions, such as redness and swelling, 
tended to be more commonly reported with JI administration. Four 
post-vaccination hypersensitivity reactions were observed.
CONCLUSIONS: Evaluations of the primary endpoint of PRNT antibody responses do 
not support alternative strategies of administering MVA vaccine by S&N on 
compressed schedules or administration by JI on the standard schedule.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01827371.