Evaluation of the Safety and Immune Response of Four Admixtures of a Tetravalent Dengue Virus Vaccine

Dengue viruses cause dengue fever and the more severe condition, dengue hemorrhagic
fever/shock syndrome. Dengue viruses are common in most tropical and subtropical regions of
the world and infection with dengue viruses is the leading cause of hospitalization and
death in children in many tropical Asian countries. For these reasons, the World Health
Organization (WHO) has made the development of a dengue virus vaccine a top priority. This
study will evaluate the safety and immunogenicity of four versions of a live, attenuated,
tetravalent dengue virus vaccine called TetraVax-DV.

This study will enroll healthy adults 18-50 years old. Participants will be randomly
assigned to receive one of the four versions of TetraVax-DV or placebo. At the vaccination
study visit, participants will undergo a medical history review, physical examination, blood
and urine collection, and vital sign measurements. Participants will then receive one
injection of their assigned vaccine or placebo in the upper arm. After receiving the
vaccine, participants will remain in the clinic for 30 minutes for observation. At home,
participants will monitor and record their temperature three times a day for 16 days.
Additional study visits will occur at Days 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 42, and 180
for physical exams, assessment of symptoms, and blood and urine collection.

Participants who received one of the four versions of the vaccine will be asked to take part
in an optional substudy that will evaluate the safety and immunogenicity of a second
vaccination 6 months after the first vaccination. In the substudy, participants will be
randomly assigned to receive either the same vaccine they received in the first part of the
study or a placebo vaccine. For 6 months following the second vaccination, participants will
attend study visits and take part in the same study procedures that occurred in the first
part of the study.