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Zika VirusPhase 1NCT06805487

Evaluation of the Protective Efficacy of TV003 or Previous Zika Infection Against Infection With ZIKV-SJRP Challenge Compared to DENV and ZIKV-naïve Controls Against Infection With ZIKV-SJRP Challenge

A Phase 1 study testing TetraVax-DV-TV003 (TV003), Plasmalyte and Challenge virus ZIKV-SJRP/2016-184 in people with Zika Virus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Zika virus (ZIKV) is an illness people can get from mosquitoes. The infection is generally mild with symptoms that include a fever, rash, red eyes, and joint pain, though most of those infected have no symptoms. Read more about this study

Who is it for?
Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for
Zika Virus
What is being tested?
TetraVax-DV-TV003 (TV003), Plasmalyte and Challenge virus ZIKV-SJRP/2016-184
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
27 participants
Where
2 sitesUnited States
Study dates
24 Sep 2024to 15 Sep 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 40 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Adults between 18 and 40 years of age, inclusive.
  • Good general health as determined by physical examination, laboratory screening, and review of medical history.
  • Available for the duration of the study, approximately 52 weeks.
  • Willingness to participate in the study as evidenced by signing the informed consent document.
  • Must be able to complete the informed consent process and comprehension assessment independently and without assistance.
  • Subjects assigned male at birth: Willingness to use barrier contraception during cervico-vaginal, anal, and oral intercourse from Study Day 0 through 90 days post ZIKV challenge (in accordance with CDC guidance).
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  • Subjects assigned female at birth: Willingness to use barrier contraception during cervico-vaginal, anal, and oral intercourse from Study Day 0 through 56 days post ZIKV challenge (in accordance with CDC guidance).
  • Subjects of childbearing potential must be willing to use effective contraception through 56 days post-ZIKV challenge, in accordance with CDC guidance. Reliable methods of contraception include hormonal birth control* (implantable, hormonal patch, hormonal vaginal ring, oral contraception, Depo-Provera injection, etc.), surgical sterilization (hysterectomy, tubal ligation, or tubal coil at least 3 months prior to inoculation with TV003/PlasmaLyte and/or ZIKV challenge), and intrauterine device. All subjects assigned female at birth will be considered having child-bearing potential except for those with post-menopausal status documented as at least 1 year since last menstrual period, those assigned female at birth who have sex with partners assigned female at birth (exclusively) and have no intention of conceiving a child during the study, and for the vaccination phase of the study only, participants who practice abstinence (≥ 6 months with no sexual contact). Subjects who are not considered to be of childbearing potential will not be required to use contraception other than barrier contraception for the purpose of reducing potential transmission.
  • Volunteers on hormonal birth control must not be on medications or other agents that decrease the effectiveness of hormonal birth control.
  • Currently enrolled in the study.
  • Good general health as determined by physical examination and review of medical history.
  • Available for the duration of the study, which is approximately 26 weeks after challenge.
  • If the challenge portion of the study is expected to begin from March 16-October 30, subject is willing to reside in the inpatient unit for 6 days (or longer for safety if necessary) following receipt of ZIKV.
  • Willingness to participate in the study as evidenced by signing the informed consent document.
  • Female assigned at birth only: Female assigned at birth subjects of childbearing potential should be willing to use highly effective contraception for the duration of the trial. Reliable methods of contraception include hormonal birth control, surgical sterilization, and intrauterine device. All female assigned at birth subjects will be considered as having childbearing potential in this phase of the study, except for those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or who are considered to be post-menopausal, as documented by at least 1 year since last menstrual period.
  • Additional Inclusion Criteria for Arm 2 Subjects with a Previous History of ZIKV Infection Only:
  • -History or serologic evidence of previous ZIKV or identified as an infectivity control.

Who cannot join

  • Currently pregnant, as determined by positive beta-human choriogonadotropin (b-hCG) test, breast-feeding, planning to become pregnant during the 12-month duration of the study or planning to donate eggs through 56 days post ZIKV challenge. A careful detailed reproductive and contraception use history will be obtained and the subject will be excluded if the history or clinical record raises concerns related to pregnancy prevention.
  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies.
  • Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the requirements of the study protocol.
  • Evidence of recent opiate use based on urine toxicology screen.
  • Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), ALT, and serum creatinine, as defined in this protocol.
  • Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.
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  • Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by subject history.
  • History of a severe allergic reaction or anaphylaxis.
  • Severe asthma (emergency room visit or hospitalization within the last 6 months).
  • HIV infection, by screening and confirmatory assays.
  • Hepatitis C virus (HCV) infection, by screening and confirmatory assays.
  • Hepatitis B virus (HBV) infection, by Hepatitis B surface antigen (HBsAg) screening.
  • History of Guillain-Barré syndrome (GBS).
  • History of seizure disease or peripheral neuropathy.
  • History of any neuroinflammatory disorder, i.e., Bell's Palsy, transverse myelitis.
  • Any known immunodeficiency syndrome, including that caused by malignancy.
  • Use of anticoagulant medications, (use of antiplatelet medication such as aspirin or non-steroidal anti-inflammatory medication is permitted and will not exclude a subject from enrollment).
  • Use of corticosteroids (excluding topical, inhaled, or nasal) or immunosuppressive drugs within 28 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as ≥10 mg prednisone equivalent per day for ≥14 days.
  • Receipt of a live vaccine within 28 days or an inactivated or subprotein vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 28 days following vaccination with the exception of the inactivated influenza vaccine and COVID 19 vaccines either licensed or under EUA which can be given at any time, however all effort will be made to avoid giving influenza and COVID-19 vaccines within the above windows.
  • Asplenia.
  • Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination.
  • Anticipated receipt of any investigational agent in the 28 days before or after vaccination.
  • Subject has definite plans to travel to a ZIKV endemic or dengue endemic area during the study.
  • Previous hypersensitivity to any study product component.
  • Refusal to allow storage of specimens for future research.
  • Subject is a JHU student currently enrolled in a coursework, an internship, or clinical hours where the supervisor or instructor of record is employed by the Center.
  • Subject is faculty or staff currently employed by the Center.
  • Additional Exclusion Criteria for TV003/PlasmaLyte Group Only:
  • History or serologic evidence of previous ZIKV, dengue virus infection, yellow fever virus, St. Louis encephalitis virus, or West Nile virus.
  • Previous receipt of a flavivirus vaccine (licensed or experimental).
  • Female assigned at birth only: Currently pregnant, as determined by positive B- HCG test, or breast-feeding.
  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease based on history, physical examination, and/or laboratory studies.
  • Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, or would render the subject unable to comply with the protocol.
  • History of a severe allergic reaction or anaphylaxis.
  • Any known immunodeficiency syndrome.
  • HIV infection, by screening and confirmatory assays (performed within 14 days of ZIKV challenge).
  • Hepatitis C virus (HCV) infection, by screening and confirmatory assays.
  • Hepatitis B virus (HBV) infection, by Hepatitis B surface antigen (HBsAg) screening.
  • Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).
  • Use of corticosteroids (excluding topical, inhaled, or nasal) or immunosuppressive drugs within 28 days prior to or following challenge. An immunosuppressive dose of corticosteroids is defined as ≥ 10 mg of a prednisone equivalent per day for ≥14 days.
  • Receipt of a live vaccine within 28 days or an inactivated or subprotein vaccine within the 14 days prior to inoculation or anticipated receipt of any vaccine during the 28 days following inoculation with the exception of the inactivated influenza vaccine and COVID-19 vaccines either licensed or under EUA which can be given at any time, however all effort will be made to avoid giving influenza and COVID-19 vaccines within the above windows.
  • Asplenia.
  • Receipt of blood products within the past 6 months, including transfusions or immunoglobulin, or anticipated receipt of any blood products or immunoglobulin during the 28 days following challenge.
  • Anticipated receipt of any other investigational agent in the 28 days before or after challenge.
  • Definite plans to travel to a dengue-endemic area during the remainder of the study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Center for Immunization Research, Johns Hopkins School of Public Health

    Baltimore, Maryland, 21205

  • Center for Immunization Research

    Baltimore, Maryland, 21224

Other trials in United States

About this study

Official title: A Phase 1 Evaluation of the Protective Efficacy of a Single Dose of the Live Attenuated Tetravalent Dengue Vaccine TV003 or Previous Zika Infection Against Infection With ZIKV-SJRP Challenge Compared to DENV and ZIKV-naïve Historical Controls Against Infection With ZIKV-SJRP Challenge

Zika virus (ZIKV) is an illness people can get from mosquitoes. The infection is generally mild with symptoms that include a fever, rash, red eyes, and joint pain, though most of those infected have no symptoms. Preventing ZIKV is important because if a pregnant person is infected with ZIKV, it can cause birth defects in their unborn child.

The goals of this study are to find out if people who have already been infected with one type of ZIKV can get infected with ZIKV a second time, and to test the ability of the TV003 dengue vaccine to prevent people from getting infected with the ZIKV-SJRP challenge virus.

Read the detailed description

This study is an open label with 2 study arms. Arm 1 will evaluate the protective efficacy of TV003 against ZIKV challenge. Arm 1 will include infectivity controls who will receive PlasmaLyte (the TV003 diluent) and the treatment assignment will be blinded to reduce bias in the assessment of adverse events. The PlasmaLyte recipients will serve as infectivity controls to ensure the potency of the ZIKV challenge. The treatment assignment of the infectivity controls may be unblinded as early as 28 days after receipt of TV003/PlasmaLyte if they are needed for ZIKV-challenge of volunteers in Arm 2 and may be challenged earlier than the TV003 cohort. Arm 2 will evaluate the protective efficacy of previous ZIKV infection against subsequent ZIKV challenge. Both arms will be compared to historical controls who previously received ZIKV infection. Infectivity controls will not be included in the efficacy analysis.

This study will include 16 flavivirus-naïve subjects for Arm 1. Twelve subjects will receive the live attenuated dengue vaccine candidate TV003 at Study Day 0 and 4 subjects will receive PlasmaLyte at Study Day 0. These subjects will be randomized in blocks of 4 (3 TV003:1 PlasmaLyte). At Study Day 180, Arm 1 subjects will receive the controlled human infection strain of ZIKV SJRP/2016-184 as a challenge virus. These subjects will include those volunteers who received TV003 and at least 1 of the infectivity controls who received PlasmaLyte. Subjects in Arm 1 will be followed for approximately 52 weeks (approximately 360 days) from the time of vaccination.

Ten subjects who had a ZIKV infection, either from a previous ZIKV controlled human infection study where they had received either ZIKV SJRP/2016-184 or ZIKV Nicaragua/2016 or were excluded during screening for previous studies as having ZIKV infection, will be enrolled as a group in Arm 2. Subjects enrolled in Arm 2 will be challenged with the ZIKV SJRP/2016-184 challenge virus separately from TV003 recipients. At least 1 of the PlasmaLyte recipients enrolled in Arm 1 on Day 0 will be included in this group to receive ZIKV SJRP/2016-184 as an infectivity control. Arm 2 subjects will be followed after ZIKV challenge for approximately 26 weeks (approximately 180 days). Subjects will be screened for eligibility up to 60 days prior to vaccination on Study Day 0.

Conditions
Zika Virus
Being tested
TetraVax-DV-TV003 (TV003), Plasmalyte, Challenge virus ZIKV-SJRP/2016-184
Medical subject headings
Zika Virus Infection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TetraVax-DV-TV003 (TV003)Biological

    0.5 ml of TV003 delivered via subcutaneous injection. TV003 contains 10^3.3 plaque forming units (PFU)/mL of rDEN1Δ30, 10^3.3 PFU/mL of rDEN2/4Δ30(ME), 10^3.3 PFU/mL of rDEN3Δ30/31- 7164 and 10^3.3 PFU/mL of rDEN4Δ30

  • PlasmalyteBiological

    0.5 mL of PlasmaLyte delivered via subcutaneous injection

  • Challenge virus ZIKV-SJRP/2016-184Biological

    0.5 ml of ZIKV-SJRP/2016-184 delivered via subcutaneous injection. ZIKV-SJRP/2016-184 contains a dose of 10^2 plaque-forming units (PFU).

Study groups in NCT06805487
Study groupRoleWhat they receive
Arm 1: DENV/ZIKV naive subjects receiving TV003ExperimentalTwelve volunteers will receive TV003 followed by challenge with ZIKV on Day 180 (6 months post-vaccination).
Receives: Biological: TetraVax-DV-TV003 (TV003); Biological: Challenge virus ZIKV-SJRP/2016-184
Infectivity Controls: DENV/ZIKV naive subjects receiving PlasmaLytePlacebo comparatorFour volunteers will receive PlasmaLyte as control followed by challenge with ZIKV at least 28 days after vaccination.
Receives: Biological: Plasmalyte; Biological: Challenge virus ZIKV-SJRP/2016-184
Arm 2: Subjects with previous ZIKV infectionExperimentalPrevious ZIKV-infected volunteers will be challenged with ZIKV on Arm 2 Day 0.
Receives: Biological: Challenge virus ZIKV-SJRP/2016-184

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence, magnitude, and duration of infectious ZIKV-SJRP/2016-184 recovered from serum following administration of ZIKV-SJRP/2016-184 in subjects who received TV003

    Compared to historical controls

    Measured: Through 180 days post challenge

  2. Incidence, magnitude, and duration of infectious ZIKV-SJRP/2016-184 recovered from serum following administration of ZIKV-SJRP/2016-184 in ZIKV-exposed subjects

    Compared to historical controls

    Measured: Through 180 days post challenge

  3. Proportion of subjects who received TV003 who develop clinical signs/symptoms of Zika infection

    Compared to historical controls

    Measured: Through 180 days post challenge

  4. Proportion of subjects who were previously infected with ZIKV who develop clinical signs/symptoms of Zika infection

    Compared to historical controls

    Measured: Through 180 days post challenge

  5. Frequency of immediate, systemic, and local adverse events (AEs) following vaccination with TV003

    Measured: Through 28 days post vaccination

  6. Frequency of immediate, systemic, and local AEs following inoculation with ZIKV-SJRP/2016-184

    Measured: Through 28 days post challenge

Secondary outcomes (10)

  1. Incidence, magnitude, and duration of ZIKV viremia induced by administering 10^2 PFU of ZIKV-SJRP/2016-184 in subjects who received TV003

    Measured by quantitative polymerase chain reaction (PCR) induced, compared to historical controls.

    Measured: Through 6 months post challenge

  2. Incidence, magnitude, and duration of ZIKV viremia induced by administering 10^2 PFU of ZIKV-SJRP/2016-184 in previously ZIKV-exposed subjects

    Measured by quantitative PCR induced, compared to historical controls.

    Measured: Through 6 months post challenge

  3. Number of TV003 vaccinees infected with DENV-1, DENV-2, DENV-3, and DENV-4 following administration of TV003

    Infection is defined as recovery of vaccine virus from the blood or serum of a subject and/or by seropositivity to DENV measured by quantitative PCR

    Measured: Through 270 days post vaccination

  4. Peak neutralizing antibody titer (NT) to DENV-1, DENV-2, DENV-3, and DENV-4

    Measured by the NT50 at 28, 56, and 90 days after TV003 vaccination.

    Measured: Through 90 days post vaccination

  5. Peak NT to ZIKV-SJRP/2016-184

    Measured by NT50 at 0, 28, 56, and 90 days post-administration of ZIKV-SJRP

    Measured: Through 90 days post challenge

  6. Number of volunteers who become infected following primary ZIKV-SJRP administration

    Measured: Through 16 days post challenge

  7. Peak NT50 against ZIKV following TV003 vaccination correlates with protection against ZIKV infection

    Measured: Through 90 days post challenge

  8. Evaluate boost in neutralizing antibody titers to DENV-1, DENV-2, DENV-3, and DENV-4 post-ZIKV challenge in subjects who received TV003

    Peak NT50 achieved through 90 days post-ZIKV challenge in TV003 recipients. A boost in antibody titer is defined as a ≥ 4-fold rise through 90 days post challenge compared with the titer just prior to ZIKV challenge.

    Measured: Through 90 days post challenge

  9. Evaluate boost in neutralizing antibody titers to ZIKV post challenge in subjects with previous ZIKV infection

    Peak NT50 achieved through 90 days post-ZIKV challenge. A boost in antibody titer is defined as a ≥ 4-fold rise in peak ZIKV neutralizing antibody titer through 90 days post challenge compared with the ZIKV neutralizing antibody titer in serum collected just prior to ZIKV challenge.

    Measured: Through 90 days post-ZIKV challenge of previous ZIKV recipients

  10. Quantity and duration of ZIKV in blood, cervico-vaginal secretions and semen

    Measured by culture (infectious virus) and by reverse transcriptase - PCR in all participants receiving ZIKV-SJRP/2016-184

    Measured: Through 6 months post challenge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2025
  2. Study start24 Sep 2024
  3. Primary completion15 Sep 2025
  4. Study completion15 Sep 2025

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06805487
Sponsor's protocol ID
CIR 369
Status last verified
Mar 2026
First submitted
28 Jan 2025
Last updated
9 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pierce KK, Durbin AP, Walsh MR, Carmolli M, Sabundayo BP, Dickson DM, Diehl SA, Whitehead SS, Kirkpatrick BD. TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies. J Clin Invest. 2024 Feb 1;134(3):e173328. doi: 10.1172/JCI173328.

    PubMed 37971871

  • Durbin AP, Kirkpatrick BD, Pierce KK, Schmidt AC, Whitehead SS. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine. Vaccine. 2011 Sep 23;29(42):7242-50. doi: 10.1016/j.vaccine.2011.07.023. Epub 2011 Jul 21.

    PubMed 21781997

  • Kallas EG, Cintra MAT, Moreira JA, Patino EG, Braga PE, Tenorio JCV, Infante V, Palacios R, de Lacerda MVG, Batista Pereira D, da Fonseca AJ, Gurgel RQ, Coelho IC, Fontes CJF, Marques ETA, Romero GAS, Teixeira MM, Siqueira AM, Barral AMP, Boaventura VS, Ramos F, Elias Junior E, Cassio de Moraes J, Covas DT, Kalil J, Precioso AR, Whitehead SS, Esteves-Jaramillo A, Shekar T, Lee JJ, Macey J, Kelner SG, Coller BG, Boulos FC, Nogueira ML. Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults. N Engl J Med. 2024 Feb 1;390(5):397-408. doi: 10.1056/NEJMoa2301790.

    PubMed 38294972

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TetraVax-DV-TV003 (TV003), Plasmalyte and Challenge virus ZIKV-SJRP/2016-184 in people with Zika Virus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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 17 inclusion and 45 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 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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. Some participants in this study may receive a placebo. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence, magnitude, and duration of infectious ZIKV-SJRP/2016-184 recovered from serum following administration of ZIKV-SJRP/2016-184 in subjects who received TV003 (time frame: Through 180 days post challenge). The study lists 6 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 NCT06805487, which also lists 3 linked publications.

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 9 Mar 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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