The purpose of this study is to compare the immune responses of two different doses (1.0 mg and 2.0 mg) and two different dosing schedules (two doses or three doses) of a mixed Hantaan virus (HTNV) and Puumala virus (PUUV) DNA vaccine in healthy participants. To maintain a blind, participants in the two-dose group will receive one dose of normal saline placebo. All of the groups will also receive a booster dose 6 months after first vaccination. The results will help to determine which dose and vaccination schedule will be best to move forward in the vaccine development process.
The study will enroll 4 randomized groups of 30 subjects each for a total of 120 subjects. These groups will be split so that 60 individuals receive the 1.0 mg dose and the other 60 receive the 2.0 mg dose. Every subject will receive a total of 3 injections on Days 0, 28, and 56. Half of each of these groups (n = 30) will receive 2 vaccine injections at Days 0 and 56 (normal saline placebo on Day 28) while the other half will receive 3 vaccine injections at Days 0, 28, and 56. All subjects will receive a booster dose at Day 168 to help assess immunogenicity with this booster dose. All doses will be administered with the TDS-IM device. All subjects will be followed until at least Day 252 (a 12 month follow-up visit may be requested). Subjects will complete post-injection memory aids for 7 days after each injection. There will also be up to 12 alternates enrolled and used to replace any original subject who fails to complete all 3 scheduled primary injections and Day 70 follow-up visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
130
HTNV/PUUV DNA vaccine mixture, composed of pWRG/HTN-M(co) and pWRG/PUU-M(s2)
0.9% sodium chloride
The TDS-IM is an integrated, fully automated clinical EP system designed for delivering DNA-based vaccines and therapies to target tissues, through temporary disruption of cellular membranes via electrical pulses
Walter Reed Army Institute of Research Clinical Trials Center
Silver Spring, Maryland, United States
Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA50
The primary endpoint will be to determine the seroconversion rates of the vaccines. Seroconversion is defined as production of neutralizing antibody titers measured using a pseudovirion neutralization assay (PsVNA). A PsVNA50 titer ≥ 20 is considered positive. Sera were collected on Days 0, 28, 56, 84, 140, 168, 196, 252, 365 and evaluated for the presence of neutralizing antibodies using PsVNA50. Percentages for seroconversion are based on the number of subjects presenting non-missing data.
Time frame: Study Days 0 to 365
Number of Solicited Adverse Events (AEs) in Study Subjects
The nature, frequency, and severity of solicited adverse events (AE) occurring from the time of each injection through 14 days following the procedure. The total number of events counts all solicited adverse events for all subjects. Subjects may have more than one solicited adverse event per body system and preferred term.
Time frame: The time of each injection through 14 days following the procedure
Number of Participants With Seroconversion of HTNV and PUUV Using PsVNA80
Seroconversion is defined as production of neutralizing antibody titers measured using a pseudovirion neutralization assay (PsVNA). Sera were collected on Days 0, 28, 56, 84, 140, 168, 196, 252, 365 and evaluated for the presence of neutralizing antibodies by using PsVNA80. Percentages for seroconversion are based on the number of subjects presenting non-missing data.
Time frame: Study Days 0 to 365
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