Response To Dengue ExposurePhase 1NCT05691530
Trial to Model Primary, Secondary, and Tertiary Dengue Using a Monovalent Vaccine
A Phase 1 study testing rDEN3Δ30/31-7164 in people with Response To Dengue Exposure, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial 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, dengue vaccines are limited and do not protect all people equally. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Response To Dengue Exposure
- What is being tested?
- rDEN3Δ30/31-7164
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2023to 27 Oct 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- To be eligible to participate in this study, an individual must meet all the following criteria:
- Aged 18 to 59 years.
- In good general health as evidenced by medical history, physical examination, and laboratory screening results.
- Willing to allow storage of samples and data for future research.
- Willing to forgo receipt of any vaccine in the 28 days preceding the vaccine or in the 28 days following the dose of vaccine. For participants opting for lymph node (LN) fine needle aspiration (FNA) on day 57, they must be willing to forgo any vaccine through final LN FNA.
- For individuals who can become pregnant: use of at least one method of highly effective contraception from the invitation to participate in the trial through day 60 after vaccination.
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- Able to provide informed consent.
- Willing to adhere to lifestyle considerations for the duration of the study.
- Willing to avoid travel to a dengue-endemic area as defined by the Centers for Disease Control and Prevention (CDC) from 1 month before vaccination through day 57
- Baseline absolute neutrophil count (ANC) > 750 cells/microL.
- Baseline creatinine < 1.5 mg/dL.
- Baseline ALT < 1.25 x upper limit of normal.
- Serologic evidence of previous dengue virus infection indicative of either one previous DENV1, 2, or 4 infection or infection with at least two different serotypes.
- For the flavivirus-naïve group, they must have no history of flavivirus vaccination, medical illness concerning for a flavivirus infection, or travel history that increases the likelihood of other flavivirus infections. If there is uncertainty about a previous flavivirus exposure, then confirmatory antibody testing against the virus of interest must be negative.
- Agree to avoid participation in other clinical studies requiring investigational interventions for the duration of this study (180 days).
- Agree to avoid blood and plasma donation outside this study through day 28.
- Contraceptive requirements: Participants who can get pregnant must agree to use highly effective contraception as outlined below from the invitation to participate in the study (approximately 2 weeks after screening) through day 60. Day 0 will be scheduled at least 28 days after the initiation of effective contraception. Participants who can get pregnant must have a negative pregnancy test on day 0 before receiving rDEN3Δ30/31-7164. If a participant becomes pregnant or suspects they are pregnant by day 60, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are:
- Intrauterine device or equivalent.
- Hormonal contraceptive (e.g., consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing).
- Condom, diaphragm, or cervical cap plus spermicide.
- A stable, long-term monogamous relationship with a partner who does not pose any potential pregnancy risk, e.g., has undergone a vasectomy at least 6 months prior to vaccination or is of the same sex as the participant.
- A hysterectomy and/or a bilateral tubal ligation, bilateral oophorectomy, or post-menopausal status defined as age >=45 years and at least 1 year since last menstrual period.
- Pregnancy after day 60 will not be exclusionary as this will not impact our primary or secondary endpoints. Although we may observe pregnancy-associated differences in the transcriptome, these endpoints are exploratory and we have chosen to prioritize safety and inclusivity for people who can become pregnant. Study blood draw volumes after day 28 are less than the recommended volumes for research blood in critically ill patients. Pregnant participants will be excluded from LN FNA due to the potential risks of anesthetics that may be used. Pregnancy testing will be performed on each LN FNA day, with a negative result required to proceed to aspiration.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pregnant at screening.
- History of or positive test result for HIV, hepatitis B, or hepatitis C.
- History of previous dengue vaccine.
- Has any of the following:
- More than 10 days of systemic immunosuppressive medications (>=10 mg prednisone dose or its equivalent) or cytotoxic medication within the 30 days prior to vaccination or immunomodulating therapy within 180 days prior to vaccination.
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- Received blood products, including immunoglobulin products, within 120 days prior to vaccination.
- History of serious reactions to vaccines.
- Hereditary, acquired, or idiopathic forms of angioedema.
- Idiopathic urticaria within the past year.
- Asthma that is not well controlled or required emergency care, urgent care, hospitalization, or intubation during the past two years or that requires the use of oral or intravenous steroids.
- Type 1 or type 2 diabetes mellitus that is not well controlled (hemoglobin A1c > 8).
- Clinically significant autoimmune disease or immunodeficiency.
- Blood pressure >= 180/110 (stage 3 hypertension) on at least 2 measures.
- Documented diagnosis of a bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
- Significant bruising or bleeding difficulties with subcutaneous injections or blood draws.
- Malignancy that is active or treated malignancy for which there is no reasonable assurance of sustained cure, or malignancy that is likely to recur during the study period.
- Asplenia or functional asplenia.
- Current alcohol or drug abuse or addiction and/or positive drug screen with substances other than marijuana.
- Any medical, psychiatric, or social condition that, in the judgement of the investigator, is a contraindication to protocol participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase 1 Trial to Model Primary, Secondary, and Tertiary Dengue Using a Monovalent Vaccine
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, dengue vaccines are limited and do not protect all people equally. One vaccine actually increased the risk of severe disease in some people and was taken off the market. Better vaccines are needed.
Read more
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.
Read the 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 rDEN3Δ30/31-7164. 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:
- 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.
- Change in DENV neutralizing antibody GMT between days 0 and 28.
- Mean peak viremia among groups as measured by viral quantitative reverse transcription polymerase chain reaction (qRT-PCR) between days 3 and 15.
Secondary Endpoints:
- Change in DENV neutralizing antibody GMT between days 0 and 57.
- DENV neutralizing antibody GMT at days 0, 28, and 57.
- Magnitude of the CD8+ T-cell response at day 15 among groups as measured by activation-induced marker (AIM) assays.
- Conditions
- Response To Dengue Exposure
- Being tested
- rDEN3Δ30/31-7164
- Keywords
- Viremia, Geometric Mean Titer, Safety, Immunogenicity, Sequential Exposure, Lymph Node Aspirates
- Medical subject headings
- Viremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rDEN3Δ30/31-7164Drug
The rDEN3Δ30/31-7164 vaccine is a live attenuated virus constructed by creating two deletions in the 3' untranslated region (UTR) of the DENV-3 Sleman/78 strain. The vaccine dose consists of 0.5 mL of 10^3.3 PFU/mL of rDEN3Δ30/31-7164 plus Plasma-Lyte A pH 7.4 diluent delivered subcutaneously into the deltoid area on day 0.
| Study group | Role | What they receive |
|---|---|---|
| Flavivirus naïve | Experimental | Participants were classified as flavivirus-naive if they met any of the following criteria: a 50% plaque reduction neutralization test (PRNT50) titer <10 for all dengue serotypes, no history of flavivirus vaccination, or no travel history associated with an increased risk of other flavivirus infections. If there was any concern regarding prior flavivirus exposure, antibody testing was performed to confirm the absence of exposure. Participants received a single 0.5 mL subcutaneous injection of 10^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0. Receives: Drug: rDEN3Δ30/31-7164 |
| Polytypic dengue virus antibody profile | Experimental | Participants were considered dengue immune if they had a 50% plaque reduction neutralization test (PRNT50) titer of ≥10 against any dengue serotype. Among these participants, those whose highest PRNT50 titer was <4-fold higher than the second-highest serotype were further categorized as follows: participants with PRNT50 titers ≥60 for at least two serotypes were classified as "polytypic", whereas those with PRNT50 titers between 10 and 60 were classified as "expanded polytypic". Participants received a single 0.5 mL subcutaneous injection of 10^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0. Receives: Drug: rDEN3Δ30/31-7164 |
| Primary Heterotypic dengue virus antibody profile | Experimental | Participants where the highest plaque reduction neutralization test (PRNT50) titer is ≥4-fold higher than the second highest serotype (or one serotype ≥10 and others <10) were considered monotypic. Of these, participants with their highest titer to DENV3 were excluded, and all others were included in the heterotypic group. Participants received a single 0.5 mL subcutaneous injection of 10^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0. Receives: Drug: rDEN3Δ30/31-7164 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Local Adverse Events (AEs)
Number of participants with at least one solicited local adverse events occurring within twenty-eight days of vaccine administration. Local reactogenicity included injection site pain, injection site tenderness, injection site bruising, injection site redness, injection site erythema, injection site swelling/induration, and injection site pruritus. Adverse events were captured by investigator examination and history from participants.
Measured: Through day 28 after vaccine administration
Number of Participants With Systemic Adverse Events (AEs)
Number of participants with systemic adverse events occurring within twenty-eight days of vaccine administration. Systemic reactogenicity events included fever, headache, eye pain (retro-orbital pain), photophobia, nausea, fatigue, myalgia, arthralgia, and maculo-papular rash (dengue-like rash). Adverse events were captured by investigator examination and history from participants.
Measured: Through day 28 after vaccine administration
Severity of Local Adverse Events (AEs) by Grade
The severity of local AEs was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials.
Grade 1: Pain, Pruritis = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness, Bruising = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity.
Grade 2: Pain, Pruritis = Some interference with activity or requires >1 dose of medication; Tenderness= Discomfort with movement; Erythema/Redness, Bruising = 5.1-10 cm; Induration/Swelling = 5.1-10 cm or interferes with activity.
Grade 3: Pain, Pruritis= Prevents daily activity and requires medical intervention; Tenderness = Significant discomfort at rest; Erythema/Redness, Bruising = > 10 cm; Induration/Swelling = > 10 cm or prevents daily activity.
Grade 4: Pain, Tenderness = Hospitalization; Erythema/Redness, Induration/Swelling = Necrosis or exfoliative dermatitis; Bruising, Pruritus: Requiring medical attention
Measured: Through day 28 after vaccine administration
Severity of Systemic Adverse Events (AEs)
The severity of systemic AEs was assessed using the grading scale below:
Grade 1: Fever = 100.4-101.1^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = No interference with activity, may require one dose of medication/treatment; Dengue-like rash: Rash is present but asymptomatic.
Grade 2: Fever = 101.2-102.0^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = Some interference with activity or requires >1 dose of medication/treatment; Dengue-like rash: Rash is symptomatic but does not interfere with activity.
Grade 3: Fever = 102.1-104^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = Prevents daily activity and requires medical intervention; Dengue-like rash: Rash is symptomatic and interferes with activity.
Grade 4: Fever = >104^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia, Dengue-like rash: Hospitalization.
Measured: Through day 28 after vaccine administration
Number of Participants With Unexpected Adverse Events (AEs)
Number of participants with unexpected adverse (AE) events occurring up to 28 days after vaccine administration of vaccine. Unexpected adverse event is defined as an AE that is not listed in the investigator's brochure at the frequency, AND specificity, AND severity that has been observed.
Measured: Through day 28 after vaccine administration
Number of Participants With Serious Adverse Events (AEs)
Number of participants with serious adverse events defined as any grade 4 or higher local or systemic adverse events based on the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials.
Local AEs: Grade 4: Pain, Tenderness = Hospitalization; Erythema/Redness, Induration/Swelling = Necrosis or exfoliative dermatitis requiring medical attention; Bruising: Hematoma requiring medical attention; Pruritis: Pruritis requiring medical attention
Systemic AEs: Grade 4: Fever = >104^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia, Dengue-like rash: Hospitalization.
Grade 5: Death
Measured: Through day 180 after vaccine administration
Mean Fold-change in Dengue virus1-4 Neutralizing Antibody Mean Titer Between Days 0 and 28
The dengue virus (DENV) geometric mean titer (GMT) is a measure of average humoral immunity against all four dengue virus (DENV1-4) serotypes before and after vaccination obtained using plaque reduction neutralization tests (PRNT). The fold change in the DENV1-4 neutralizing antibody GMT between days 0 and 28 was analyzed as GMT Day 28/GMT Day 0.
Measured: Day 28 and day 0
Mean Peak Viremia
The mean peak viremia was measured by viral quantitative reverse transcription polymerase chain reaction (qRT-PCR) for days 3, 6, 9, 12, and 15. Analysis was done as the average of the log mean of the peak value for each participant.
Measured: Day 3 through day 15
Secondary outcomes (3)
Mean Fold-change in Dengue virus1-4 Neutralizing Antibody Mean Titer Between Days 0 and 57
The dengue virus (DENV) geometric mean titer (GMT) is a measure of average humoral immunity against all four dengue virus (DENV1-4) serotypes before and after vaccination obtained using plaque reduction neutralization tests (PRNT). The fold change in the DENV1-4 neutralizing antibody GMT between days 0 and 57 was analyzed as GMT Day 57/GMT Day 0.
Measured: Day 57 and day 0
Mean Titer for Dengue Virus Neutralizing Antibody
The dengue virus (DENV) geometric mean titer (GMT) is a measure of average humoral immunity against all four dengue virus (DENV1-4) serotypes. GMT for the DENV1-4 neutralizing antibody titer was assessed for days 0, 28, and 57.
Measured: Day 0, Day 28, and Day 57
Percent Dengue-specific CD8+ T-cells
Percent dengue virus (DENV)-specific CD8+ T-cells among total CD8+ T-cells at day 15 was measured through flow cytometric analyses using the Activation-Induced Marker (AIM) assays.
Measured: Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2023
- Study start7 Mar 2023
- Primary completion23 Apr 2025
- Study completion27 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Response To Dengue ExposureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Camila D Odio, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05691530
- Sponsor's protocol ID
- 10001078
- Other IDs
- 001078-I
- Status last verified
- May 2026
- First submitted
- 19 Jan 2023
- Last updated
- 16 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Human data generated in this study may be shared for future research as follows: * De-identified data in an NIH-funded or supported public repository. * De-identified data in another public repository. * Identified data in the Biomedical Translational Research Information System (automatic for activities in the CC) and/or the NIAID Genomic Research Integration System. * De-identified data with approved outside collaborators under appropriate agreements. * De-identified data in publications and/or public presentations.
Publications
Odio CD, Lowman KE, Law M, Aogo RA, Hunsberger S, Wood BJ, Kassin M, Levy E, Callier V, Firdous S, Hasund CM, Voirin C, Kattappuram R, Yek C, Manning J, Durbin A, Whitehead SS, Katzelnick LC. Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine. BMC Infect Dis. 2023 May 23;23(1):345. doi: 10.1186/s12879-023-08299-5.
PubMed 37221466
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial to Model Primary, Secondary, and Tertiary Dengue Using a Monovalent Vaccine
- ClinicalTrials.gov ID
- NCT05691530
- Acronym / sponsor ID
- 10001078
- Conditions
- Response To Dengue Exposure
- Keywords
- Viremia, Geometric Mean Titer, Safety, Immunogenicity, Sequential Exposure, Lymph Node Aspirates
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 7 Mar 2023 (actual)
- Primary completion
- 23 Apr 2025 (actual)
- Study completion
- 27 Oct 2025 (actual)
- First posted
- 20 Jan 2023 (actual)
- Results
- Posted 28 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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, dengue vaccines are limited and do not protect all people equally. One vaccine actually increased the risk of severe disease in some people and was taken off the market. 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 rDEN3Δ30/31-7164. 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:
- 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.
- Change in DENV neutralizing antibody GMT between days 0 and 28.
- Mean peak viremia among groups as measured by viral quantitative reverse transcription polymerase chain reaction (qRT-PCR) between days 3 and 15.
Secondary Endpoints:
- Change in DENV neutralizing antibody GMT between days 0 and 57.
- DENV neutralizing antibody GMT at days 0, 28, and 57.
- Magnitude of the CD8+ T-cell response at day 15 among groups as measured by activation-induced marker (AIM) assays.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Flavivirus naïve | Experimental | Drug: rDEN3Δ30/31-7164Participants were classified as flavivirus-naive if they met any of the following criteria: a 50% plaque reduction neutralization test (PRNT50) titer <10 for all dengue serotypes, no history of flavivirus vaccination, or no travel history associated with an increased risk of other flavivirus infections. If there was any concern regarding prior flavivirus exposure, antibody testing was performed to confirm the absence of exposure. Participants received a single 0.5 mL subcutaneous injection of 10^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0. |
| Polytypic dengue virus antibody profile | Experimental | Drug: rDEN3Δ30/31-7164Participants were considered dengue immune if they had a 50% plaque reduction neutralization test (PRNT50) titer of ≥10 against any dengue serotype. Among these participants, those whose highest PRNT50 titer was <4-fold higher than the second-highest serotype were further categorized as follows: participants with PRNT50 titers ≥60 for at least two serotypes were classified as "polytypic", whereas those with PRNT50 titers between 10 and 60 were classified as "expanded polytypic". Participants received a single 0.5 mL subcutaneous injection of 10^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0. |
| Primary Heterotypic dengue virus antibody profile | Experimental | Drug: rDEN3Δ30/31-7164Participants where the highest plaque reduction neutralization test (PRNT50) titer is ≥4-fold higher than the second highest serotype (or one serotype ≥10 and others <10) were considered monotypic. Of these, participants with their highest titer to DENV3 were excluded, and all others were included in the heterotypic group. Participants received a single 0.5 mL subcutaneous injection of 10^3.3 PFU/mL rDEN3Δ30/31-7164 vaccine formulated in Plasma-Lyte A (pH 7.4) diluent in the deltoid region on day 0. |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- To be eligible to participate in this study, an individual must meet all the following criteria:
- Aged 18 to 59 years.
- In good general health as evidenced by medical history, physical examination, and laboratory screening results.
- Willing to allow storage of samples and data for future research.
- Willing to forgo receipt of any vaccine in the 28 days preceding the vaccine or in the 28 days following the dose of vaccine. For participants opting for lymph node (LN) fine needle aspiration (FNA) on day 57, they must be willing to forgo any vaccine through final LN FNA.
Key exclusion criteria (20 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pregnant at screening.
- History of or positive test result for HIV, hepatitis B, or hepatitis C.
- History of previous dengue vaccine.
- Has any of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rDEN3Δ30/31-7164The rDEN3Δ30/31-7164 vaccine is a live attenuated virus constructed by creating two deletions in the 3' untranslated region (UTR) of the DENV-3 Sleman/78 strain. The vaccine dose consists of 0.5 mL of 10^3.3 PFU/mL of rDEN3Δ30/31-7164 plus Plasma-Lyte A pH 7.4 diluent delivered subcutaneously into the deltoid area on day 0. | Drug | Flavivirus naïve, Polytypic dengue virus antibody profile, Primary Heterotypic dengue virus antibody profile |
Primary outcome
Number of Participants With Local Adverse Events (AEs)
Time frame: Through day 28 after vaccine administration
Number of participants with at least one solicited local adverse events occurring within twenty-eight days of vaccine administration. Local reactogenicity included injection site pain, injection site tenderness, injection site bruising, injection site redness, injection site erythema, injection site swelling/induration, and injection site pruritus. Adverse events were captured by investigator examination and history from participants.
Number of Participants With Systemic Adverse Events (AEs)
Time frame: Through day 28 after vaccine administration
Number of participants with systemic adverse events occurring within twenty-eight days of vaccine administration. Systemic reactogenicity events included fever, headache, eye pain (retro-orbital pain), photophobia, nausea, fatigue, myalgia, arthralgia, and maculo-papular rash (dengue-like rash). Adverse events were captured by investigator examination and history from participants.
Severity of Local Adverse Events (AEs) by Grade
Time frame: Through day 28 after vaccine administration
The severity of local AEs was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Grade 1: Pain, Pruritis = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness, Bruising = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity. Grade 2: Pain, Pruritis = Some interference with activity or requires >1 dose of medication; Tenderness= Discomfort with movement; Erythema/Redness, Bruising = 5.1-10 cm; Induration/Swelling = 5.1-10 cm or interferes with activity. Grade 3: Pain, Pruritis= Prevents daily activity and requires medical intervention; Tenderness = Significant discomfort at rest; Erythema/Redness, Bruising = > 10 cm; Induration/Swelling = > 10 cm or prevents daily activity. Grade 4: Pain, Tenderness = Hospitalization; Erythema/Redness, Induration/Swelling = Necrosis or exfoliative dermatitis; Bruising, Pruritus: Requiring medical attention
Severity of Systemic Adverse Events (AEs)
Time frame: Through day 28 after vaccine administration
The severity of systemic AEs was assessed using the grading scale below: Grade 1: Fever = 100.4-101.1^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = No interference with activity, may require one dose of medication/treatment; Dengue-like rash: Rash is present but asymptomatic. Grade 2: Fever = 101.2-102.0^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = Some interference with activity or requires >1 dose of medication/treatment; Dengue-like rash: Rash is symptomatic but does not interfere with activity. Grade 3: Fever = 102.1-104^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia = Prevents daily activity and requires medical intervention; Dengue-like rash: Rash is symptomatic and interferes with activity. Grade 4: Fever = >104^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia, Dengue-like rash: Hospitalization.
Number of Participants With Unexpected Adverse Events (AEs)
Time frame: Through day 28 after vaccine administration
Number of participants with unexpected adverse (AE) events occurring up to 28 days after vaccine administration of vaccine. Unexpected adverse event is defined as an AE that is not listed in the investigator's brochure at the frequency, AND specificity, AND severity that has been observed.
Number of Participants With Serious Adverse Events (AEs)
Time frame: Through day 180 after vaccine administration
Number of participants with serious adverse events defined as any grade 4 or higher local or systemic adverse events based on the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Local AEs: Grade 4: Pain, Tenderness = Hospitalization; Erythema/Redness, Induration/Swelling = Necrosis or exfoliative dermatitis requiring medical attention; Bruising: Hematoma requiring medical attention; Pruritis: Pruritis requiring medical attention Systemic AEs: Grade 4: Fever = >104^oF; Fatigue, Retro-orbital pain, Photophobia, Nausea, Headache, Myalgia, Arthralgia, Dengue-like rash: Hospitalization. Grade 5: Death
Mean Fold-change in Dengue virus1-4 Neutralizing Antibody Mean Titer Between Days 0 and 28
Time frame: Day 28 and day 0
The dengue virus (DENV) geometric mean titer (GMT) is a measure of average humoral immunity against all four dengue virus (DENV1-4) serotypes before and after vaccination obtained using plaque reduction neutralization tests (PRNT). The fold change in the DENV1-4 neutralizing antibody GMT between days 0 and 28 was analyzed as GMT Day 28/GMT Day 0.
Mean Peak Viremia
Time frame: Day 3 through day 15
The mean peak viremia was measured by viral quantitative reverse transcription polymerase chain reaction (qRT-PCR) for days 3, 6, 9, 12, and 15. Analysis was done as the average of the log mean of the peak value for each participant.
3 secondary outcomes
Mean Fold-change in Dengue virus1-4 Neutralizing Antibody Mean Titer Between Days 0 and 57
Time frame: Day 57 and day 0
Mean Titer for Dengue Virus Neutralizing Antibody
Time frame: Day 0, Day 28, and Day 57
Percent Dengue-specific CD8+ T-cells
Time frame: Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37221466Odio CD, Lowman KE, Law M, Aogo RA, Hunsberger S, Wood BJ, Kassin M, Levy E, Callier V, Firdous S, Hasund CM, Voirin C, Kattappuram R, Yek C, Manning J, Durbin A, Whitehead SS, Katzelnick LC. Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine. BMC Infect Dis. 2023 May 23;23(1):345. doi: 10.1186/s12879-023-08299-5.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Human data generated in this study may be shared for future research as follows: * De-identified data in an NIH-funded or supported public repository. * De-identified data in another public repository. * Identified data in the Biomedical Translational Research Information System (automatic for activities in the CC) and/or the NIAID Genomic Research Integration System. * De-identified data with approved outside collaborators under appropriate agreements. * De-identified data in publications and/or public presentations.
Related trials for Response To Dengue Exposure
Not yet recruitingPhase 3
Phase 3b Trial To Evaluate Safety And Immune Response (Superiority) of a Two-Dose Butantan-DV Regimen And The Standard Single Dose In Dengue-Naive Children/Adolescents and Immune Response (Non-inferiority) in a Manufacturing Facility Change (DEN-06-IB)
Dengue Fever With Warning Signs
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Camila D Odio, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rDEN3Δ30/31-7164 in people with Response To Dengue Exposure, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Local Adverse Events (AEs) (time frame: Through day 28 after vaccine administration). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05691530, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.