Trial to Model Primary, Secondary, and Tertiary Dengue Using a Monovalent Vaccine
- Conditions
- Response To Dengue Exposure
- Interventions
- Drug: rDENdelta30/31-7164
- Registration Number
- NCT05691530
- Brief Summary
Background:
Dengue is a disease caused by a virus transmitted by mosquitoes in tropical and subtropical regions. Dengue is a leading cause of hospital stays and death in parts of Asia and Latin America, and outbreaks have occurred in the US. Currently, only one vaccine is licensed for dengue, but it only protects people who have had dengue before. In people who have never had dengue, that vaccine increases the risk of severe disease. Better vaccines are needed.
Objectives:
To test a potential new vaccine against dengue. To see if side effects and immune responses are different depending on a person s previous exposure to dengue.
Eligibility: Healthy people aged 18 to 59 years.
Design:
Participants will visit the clinic 11 times in 7 months; 9 of those visits will be in the first 2 months. Two additional visits are optional.
Participants will be screened. They will have a physical exam with urine and blood tests. They will complete a survey about their travel history.
Participants may opt to have a lymph node aspiration before receiving the study vaccine. An area in the left armpit will be numbed. A needle will be inserted to remove some cells from a lymph node.
The vaccine will be injected into the fat under the skin of the participant s upper left arm.
Participants will return for a provider visit and blood draws every 3 days for about the first 2 weeks. Then they will return for a provider visit and blood draws after longer intervals up to 7 months. The lymph node aspiration may be repeated at later visits.
Participants may opt to return for a last visit after 12 months.
- Detailed Description
Study Description:
Phase 1 trial wherein healthy adults with no (naive), one (primary heterotypic), or more than one (polytypic) previous natural dengue virus (DENV) infection(s) will be immunized with the DENV3 monovalent vaccine rDEN3delta30/31-7164. We aim to examine how pre-vaccine host immunity influences the safety and immunogenicity of monovalent DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have evidence of infection with the vaccine strain as indicated by a significant increase in the DENV neutralizing antibody geometric mean titer (GMT) between days 0 and 28. However, due to the immunity conferred by prior dengue exposure(s), the polytypic group will have the lowest and the heterotypic group will have the highest mean peak viremia, indicating protection and enhancement, respectively. Additionally, the polytypic group will have the strongest CD8+ T-cell responses at day 15 and will only have a transient rise in GMT with no difference in GMT between days 0 and 57. In contrast, the change in GMT will persist at day 57 in the heterotypic and naive groups. Finally, we expect that prior immunity will influence the vaccine response as evidenced by a significant association between the day 0 GMT and GMT at days 28 and 57.
Primary Objective:
Evaluate the safety of monovalent DENV3 vaccination in those with distinct natural DENV infection histories living in non-endemic areas, and how prior DENV immunity influences protection against vaccine strain infection evaluated by the change in GMT and mean peak viremia.
Secondary Objective:
Further evaluate how DENV infection history impacts the immunogenicity of the vaccine.
Primary Endpoints:
1. The frequency and severity of local and systemic reactogenicity signs and symptoms during the 28-day period after each vaccination, unexpected adverse events (AEs) up to 28 days after each vaccination, and serious adverse events (SAEs) through day 180.
2. Change in DENV neutralizing antibody GMT between days 0 and 28.
3. Mean peak viremia among groups as measured by viral quantitative reverse transcription polymerase chain reaction (qRT-PCR) between days 3 and 15.
Secondary Endpoints:
1. Change in DENV neutralizing antibody GMT between days 0 and 57.
2. DENV neutralizing antibody GMT at days 0, 28, and 57.
3. Magnitude of the CD8+ T-cell response at day 15 among groups as measured by activation-induced marker (AIM) assays.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Polytypic DENV Antibody Profile rDENdelta30/31-7164 Those considered immune (a \>=70% neutralization or plaques at a 1:40 dilution) to at least two serotypes. Flavivirus Naive rDENdelta30/31-7164 Those with \<=50% neutralization at a 1:10 dilution to all four DENV serotypes, no history of flavivirus vaccination, or travel history that increases the likelihood of other flavivirus infections. Primary Heterotypic DENV Antibody Profile rDENdelta30/31-7164 Those who have a \>=70% neutralization or plaques at a 1:40 dilution for a single serotype, either DENV1, DENV2, or DENV4.
- Primary Outcome Measures
Name Time Method The frequency and severity of local and systemic reactogenicity signs and symptoms during the 28 day period after each vaccination, unexpected AEs up to 28 days after each vaccination, and SAEs through day 180. Days 28 and 180 Evaluate the safety of monovalent DENV3 vaccination in those with distinct natural DENV infection histories living in non-endemic areas, and how prior DENV immunity influences protection against vaccine strain infection evaluated by the change in GMT and mean peak viremia.
Change in the DENV neutralizing antibody GMT between days 0 and 28. Days 0 and 28 Evaluate the safety of monovalent DENV3 vaccination in those with distinct natural DENV infection histories living in non-endemic areas, and how prior DENV immunity influences protection against vaccine strain infection evaluated by the change in GMT and mean peak viremia.
Mean peak viremia among groups as measured by viral qRT-PCR between days 3 and 15. Days 3, 6, 9, 12 and 15 Evaluate the safety of monovalent DENV3 vaccination in those with distinct natural DENV infection histories living in non-endemic areas, and how prior DENV immunity influences protection against vaccine strain infection evaluated by the change in GMT and mean peak viremia.
- Secondary Outcome Measures
Name Time Method Change in DENV neutralizing antibody GMT between days 0 and 57 and days 0 and 90. Days 0, 57 and 90 Further evaluate how DENV infection history impacts the immunogenicity of the vaccine.
Change in DENV3 neutralizing antibody titer between day 0 and peak titer (measured at days 28, 57, or 90). Days 0, 28, 57 and 90 Further evaluate how DENV infection history impacts the immunogenicity of the vaccine.
DENV neutralizing antibody GMT at days 0, 28, 57, and 90. Days 0, 28, 57 and 90 Further evaluate how DENV infection history impacts the immunogenicity of the vaccine.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States