safety of and immune response to a dengue virus vaccine (rden4delta30-4995) in healthy adults

Conditions: Dengue

Summary: dengue fever, which is caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. the purpose of this study is to evaluate the safety and immune response to the dengue vaccine den4delta30-4995 in healthy adults.

dengue viruses account for more than 50 million cases of dengue fever and a half million cases of the more severe disease, dengue hemorrhagic fever/dengue shock syndrome. infection with dengue viruses is the leading cause of hospitalization and death in children in at least eight asian countries. the goal of producing a vaccine against dengue fever is to induce a long-lived antibody response against all four dengue serotypes. the rden4delta30-4995 vaccine candidate is a live attenuated recombinant virus derived from rden4delta30 for protection against dengue virus serotype 4. the purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of rden4delta30-4995 in healthy adults. this study will last 180 days (6 months). participants in cohort 1 will be randomly assigned to receive the highest dose of rden4delta30 or placebo at study entry. participants in cohort 2 will be randomly assigned to receive a lower dose of rden4delta30 or placebo. participants in cohort 3 will be randomly assigned to receive the lowest dose of rden4delta30 or placebo. cohorts 2 and 3 will begin after a safety review of all participants in the previous cohort. after initial vaccination, participants in cohort 1 will be followed every other day for the first 16 days of the study, monitoring their temperature three times a day through day 16 and recording these measurements in a diary. after day 16, study visits will occur on days 21, 28, 42, and 180 and will include a physical exam and blood collection. some participants will also be asked to undergo a skin biopsy or additional blood collection at selected visits.

Eligibility criteria:
inclusion criteria: * adult males and non-pregnant females between 18 and 50 years of age * good general health * available for the duration of the study * willing to use acceptable methods of contraception for the duration of the study exclusion criteria: * significant neurologic, cardiac, lung, liver, rheumatologic, autoimmune, or kidney disease * behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study * significant laboratory abnormalities * medical, work, or family problems as a result of alcohol or illegal drug use within 12 months prior to study entry * history of severe allergic reaction or anaphylaxis * severe asthma * hiv-1 serotype infected * hepatitis c virus (hcv) infected * hepatitis b surface antigen positive * immunodeficiency syndrome * use of corticosteroids or immunosuppressive medications within 2 weeks prior to study entry. individuals using topical or nasal corticosteroids are not excluded. * live vaccine within 4 weeks prior to study entry * killed vaccine within 2 weeks prior to study entry * absence of spleen * blood products within 6 months prior to study entry * previous dengue virus or other flavivirus (e.g., yellow fever virus, st. louis encephalitis, west nile virus) infection * prior receipt of yellow fever or dengue vaccine (licensed or experimental) * plans to travel to an area where dengue infection is common * received an investigational agent within 30 days prior to study entry * other condition that, in the opinion of the investigator, would affect participation in the study * pregnant or breastfeeding

Keywords: dengue fever dengue vaccine dengue virus dengue hemorrhagic fever dengue shock syndrome