TetraVax-DV-TV003 for Zika Virus

Recruiting at 1 trial location

Overseen By Aislinn Woody, B.S.N., R.N.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Anticoagulants, Corticosteroids, Immunosuppressives, others

Disqualifiers: Pregnancy, HIV, Hepatitis B/C, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

26 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use certain medications like corticosteroids or immunosuppressive drugs within 28 days before or after vaccination. If you are on anticoagulant medications, you may not be eligible to participate.

Is the TetraVax-DV-TV003 vaccine safe for humans?

The TetraVax-DV-TV003 vaccine has been tested in various studies and is generally well-tolerated in humans, with mild side effects like rash and headache. No serious vaccine-related adverse events were reported, indicating it is generally safe. ^{1 2 3 4 5}

Research Team

Anna Durbin, M.D.

Principal Investigator

Johns Hopkins Bloomberg School of Public Health

Eligibility Criteria

This trial is for individuals who have had Zika virus (ZIKV) before or those who haven't but received the TV003 dengue vaccine. It aims to understand if previous infection or vaccination can protect against a new ZIKV strain. Specific eligibility criteria are not provided.

Inclusion Criteria

Must be able to complete the informed consent process and comprehension assessment independently and without assistance

Good general health as determined by physical examination, laboratory screening, and review of medical history

I agree to use barrier methods during sex for 90 days after the Zika virus study starts.

Exclusion Criteria

Evidence of recent opiate use based on urine toxicology screen

Hepatitis C virus (HCV) infection, by screening and confirmatory assays

I am taking blood thinners.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 8 weeks

Treatment

Participants receive the TV003 dengue vaccine or PlasmaLyte, followed by a ZIKV challenge

6 months

Multiple visits for vaccination and monitoring

Challenge and Follow-up

Participants are challenged with ZIKV and monitored for safety and effectiveness

26 weeks

Regular follow-up visits for monitoring

Long-term Follow-up

Participants are monitored for long-term safety and immune response

52 weeks

Treatment Details

Interventions

• TetraVax-DV-TV003

Trial Overview The study tests whether prior ZIKV infection or immunization with the TV003 dengue vaccine prevents reinfection when exposed to a different ZIKV strain, known as ZIKV-SJRP/2016-184. Participants will be exposed to this challenge virus.

Participant Groups

Group I: Arm 2: Subjects with previous ZIKV infection Experimental Treatment 1 Intervention

Previous ZIKV-infected volunteers will be challenged with ZIKV on Arm 2 Day 0.

Group II: Arm 1: DENV/ZIKV naive subjects receiving TV003 Experimental Treatment 2 Interventions

Twelve volunteers will receive TV003 followed by challenge with ZIKV on Day 180 (6 months post-vaccination).

Group III: Infectivity Controls: DENV/ZIKV naive subjects receiving PlasmaLyte Placebo Group 2 Interventions

Four volunteers will receive PlasmaLyte as control followed by challenge with ZIKV at least 28 days after vaccination.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Johns Hopkins Bloomberg School of Public Health

Collaborator

Trials

441

Recruited

2,157,000+

Findings from Research

The tetravalent dengue vaccine (TDV) developed by Sanofi Pasteur was found to be safe, with no serious adverse events reported among the 66 healthy adult participants in the study.

The vaccine demonstrated strong immunogenicity, as all participants who received three doses achieved seroconversion against all four dengue virus serotypes, indicating effective immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel tetravalent dengue vaccine is well tolerated and immunogenic against all 4 serotypes in flavivirus-naive adults. Morrison, D., Legg, TJ., Billings, CW., et al.[2010]

The live attenuated tetravalent dengue vaccine candidate (TV003) was well tolerated in a study of 58 individuals with prior flavivirus exposure, showing only mild adverse events, primarily rash.

After one dose of TV003, 87% of participants developed a strong immune response with neutralizing antibodies against all four dengue serotypes, indicating that a single dose may be sufficient for protection against dengue disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination. Whitehead, SS., Durbin, AP., Pierce, KK., et al.[2018]

The tetravalent dengue vaccine (TDV) was found to be well tolerated among 360 healthy volunteers aged 1.5 to 45 years, with only mild adverse events like injection site pain and itching reported more frequently than with placebo.

TDV demonstrated strong immunogenicity, achieving over 95% seropositivity for dengue serotypes 1-3 and between 72.7% to 100% for serotype 4 after two doses, indicating its potential effectiveness in providing immunity against dengue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study. Sirivichayakul, C., Barranco-Santana, EA., Esquilin-Rivera, I., et al.[2016]

TAK-003, a dengue tetravalent vaccine, has shown a good safety profile in a large study involving 14,627 participants aged 4-60, with fewer serious adverse events compared to the placebo group (6% vs 8%).

The vaccine was well tolerated across different age groups, with mild injection site reactions being the most common side effects, and no significant safety risks were identified, making it a promising option for dengue prevention regardless of previous exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live Attenuated Vaccine Candidate. Patel, SS., Rauscher, M., Kudela, M., et al.[2023]

Dengvaxia (CYD-TDV) is the first dengue vaccine approved by the US FDA, showing efficacy in preventing severe secondary dengue infections, particularly in individuals with prior dengue exposure.

The review highlights that the vaccine's effectiveness varies based on seroprevalence, serotypes, and age, suggesting that it can be integrated into global vaccination strategies to combat dengue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dengvaxia: the world's first vaccine for prevention of secondary dengue. Tully, D., Griffiths, CL.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

A novel tetravalent dengue vaccine is well tolerated and immunogenic against all 4 serotypes in flavivirus-naive adults. [2010]

2. United States pubmed.ncbi.nlm.nih.gov

In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live Attenuated Vaccine Candidate. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Dengvaxia: the world's first vaccine for prevention of secondary dengue. [2021]