Vaccine for Zika

Recruiting at 3 trial locations

Overseen By Chief Medical Officer

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Valneva Austria GmbH

Must not be taking: Immunosuppressants, Cytotoxic drugs

Disqualifiers: Flavivirus history, HIV, Hepatitis, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 399

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 1 clinical trial consists of an initial open-label sentinel run-in (n=25) and a randomized, double-blind, dose-finding (n=125) investigating three antigen dose levels (low, medium and high) of VLA1601 and bedside mixing of the low-dose formulation with one of the two additional adjuvants (CpG1018®, 3M-052-AF/AP 60-702). VLA1601 will be administered according to a two-dose regimen (i.e., on Day 1 and Day 29). The primary objective of this trial is to assess the safety and tolerability of the vaccine candidate up to 7 days after each vaccination; and to assess the immune response induced by the vaccine candidate 28 days after the second vaccination. Additionally, safety and immune response of the vaccine candidate will be monitored throughout the trial.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immuno-suppressive therapy, you must have stopped it at least 4 weeks before the first vaccination.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immuno-suppressive therapy, you must have stopped it at least 4 weeks before the first vaccination. It's best to discuss your specific medications with the trial investigator.

What data supports the idea that Vaccine for Zika (also known as: VLA1601, VLA1601) is an effective treatment?

The available research shows that the Vaccine for Zika, specifically a non-integrating lentiviral vector (NILV)-based vaccine, has been effective in providing protection against the Zika virus. In studies with mice, a single dose of this vaccine led to strong immune responses and full protection against the virus within just 7 days. This protection lasted for at least 6 months, indicating long-lasting immunity. Additionally, a purified inactivated virus (ZPIV) vaccine was found to be safe and able to trigger an immune response in humans, suggesting its potential effectiveness. These findings suggest that the Vaccine for Zika could be a promising option for preventing Zika virus infections. ^{1 2 3 4 5}

What safety data exists for the Zika vaccine?

The Zika purified inactivated virus (ZPIV) vaccine has been evaluated in several phase-1 clinical trials, showing it to be well tolerated and immunogenic in humans. Adverse events were mostly local, such as injection site pain, erythema, and itching, with some systemic effects like fever, myalgia, nausea, and fatigue. The vaccine demonstrated a range of immunogenicity, with seroconversion rates varying from 10% to 100% depending on the vaccine type and dosage. Overall, the candidate vaccines were found to be relatively safe, especially at higher doses. ^{1 2 3 6 7}

Is the Zika vaccine safe for humans?

The Zika vaccine has been tested in early human trials and found to be generally safe. Most side effects were mild, like pain or redness at the injection site, fever, muscle pain, nausea, and tiredness. ^{1 2 3 6 7}

Is VLA1601 a promising treatment for Zika?

The information provided does not mention VLA1601 specifically, so we cannot determine if it is a promising treatment for Zika based on the given research articles. ^{1 2 5 8 9}

How is the VLA1601 treatment for Zika different from other treatments?

VLA1601 is a unique vaccine candidate for Zika because it is based on a highly attenuated poxvirus vector, which is designed to express Zika virus structural proteins and induce a strong immune response. Unlike other treatments, it aims to provide protection through a single dose, potentially offering a rapid and durable defense against the virus. ^{1 2 5 8 9}

Eligibility Criteria

This trial is for healthy adults who can participate in a study testing a new Zika virus vaccine. Participants will receive two doses of the vaccine, with some getting additional ingredients to boost their immune response.

Inclusion Criteria

I agree to use birth control for 3 months after my last vaccine dose.

BMI of ≥18.5 and <30 kg/m2

Generally healthy as determined by the investigator's clinical judgement based on medical history, physical examination, and screening laboratory tests

Exclusion Criteria

Tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)

With a history of severe hypersensitivity reactions or anaphylaxis

With a history of any vaccine related contraindicating event

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Open-label Run-in

Initial open-label sentinel run-in phase with staggered dose-escalation for 25 participants

4 weeks

2 visits (in-person)

Randomized Treatment

Randomized, double-blind, dose-finding phase with two vaccinations on Day 1 and Day 29

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and immune response up to 6 months after the second vaccination

6 months

Phone calls and on-site visit at Day 395 for selected participants

Treatment Details

Interventions

• VLA1601

Trial Overview The trial is examining three different dose levels of VLA1601, a Zika virus vaccine candidate, mixed with adjuvants CpG1018® or 3M-052-AF/AP 60-702. The goal is to find the safest and most effective dose for inducing an immune response.

Participant Groups

Group I: VLA1601 Medium dose Experimental Treatment 1 Intervention

Group II: VLA1601 Low dose + CpG 1018® Experimental Treatment 2 Interventions

Group III: VLA1601 Low dose + 3M-052-AF Experimental Treatment 2 Interventions

Group IV: VLA1601 Low dose Experimental Treatment 1 Intervention

Group V: VLA1601 High dose Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Valneva Austria GmbH

Lead Sponsor

Trials

46

Recruited

59,100+

Findings from Research

Multiple Zika vaccine platforms, including inactivated virus and nucleic acid vaccines, are currently in human clinical trials, showing promising results from recent phase I trials.

Despite a decrease in transmission rates, Zika virus remains endemic in the Americas, highlighting the urgent need for continued vaccine development to prepare for potential future outbreaks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development. Castanha, PMS., Marques, ETA.[2021]

Zika virus, which caused a public health emergency due to its association with microcephaly in newborns, has prompted urgent efforts to develop vaccines, with various strategies being explored including live attenuated, inactivated, DNA, and viral vectored vaccines.

The first clinical trials for Zika virus vaccine candidates were set to begin in late 2016, but the process for getting a vaccine approved is expected to take several years, highlighting the need for accelerated development to ensure timely availability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine Development for Zika Virus-Timelines and Strategies. Durbin, AP.[2018]

The Zika purified inactivated virus (ZPIV) vaccine was found to be safe and well tolerated in healthy adults, with no serious treatment-related adverse events reported during a 52-week follow-up period.

Immunogenicity of ZPIV required two doses for effective antibody response, with the standard regimen showing the highest peak neutralizing antibody levels, but antibody levels declined significantly after 16 weeks, indicating the need for further studies to optimize dosing schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial. Stephenson, KE., Tan, CS., Walsh, SR., et al.[2023]

Researchers have made significant progress in developing various Zika virus vaccine candidates, including inactivated virus, live attenuated virus, and viral vector vaccines, with many advancing to clinical trials.

The primary goal of Zika vaccination is to prevent the transmission of the virus from pregnant women to their unborn babies, necessitating unique safety and efficacy standards for these vaccines compared to those for other diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in Zika Virus Vaccines. Garg, H., Mehmetoglu-Gurbuz, T., Joshi, A.[2023]

The engineered NILV-based Zika vaccine demonstrated strong immunogenicity, producing robust neutralizing antibodies and providing full protection against Zika virus in mouse models just 7 days after a single dose.

This vaccine also conferred long-lasting immunity, remaining effective even 6 months post-immunization, highlighting its potential as a rapid and durable solution for Zika virus outbreaks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single Dose of NILV-Based Vaccine Provides Rapid and Durable Protection against Zika Virus. Ku, MW., Anna, F., Souque, P., et al.[2021]

In a systematic review of five phase-1 clinical trials involving candidate anti-Zika vaccines, all vaccines demonstrated high immunogenicity, with seroconversion rates ranging from 10% to 100%, particularly showing the highest rates for DNA vaccines after multiple doses.

The candidate vaccines were generally well-tolerated, with most adverse events being mild and localized, such as injection site pain, while systemic effects like fever and fatigue were also reported, indicating a favorable safety profile for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of Zika virus vaccine: A systematic review of clinical trials. Yeasmin, M., Molla, MMA., Masud, HMAA., et al.[2023]

Zika virus infection can lead to serious health issues, including Congenital Zika Syndrome, which has prompted urgent efforts to develop vaccines and treatments, especially following the 2015 epidemic.

Research has shown that various vaccine candidates are safe and can generate immune responses in early human trials, but the decline in Zika transmission has hindered the ability to conduct trials that measure their effectiveness in preventing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zika vaccine pre-clinical and clinical data review with perspectives on the future development. Thomas, SJ., Barrett, A.[2023]

The novel Zika virus vaccine, MVA-ZIKV, developed using a modified vaccinia virus, effectively produced neutralizing antibodies and strong CD8+ T cell responses in mice, indicating its potential for robust immune protection.

A single dose of MVA-ZIKV significantly reduced viral levels in immunocompromised mice infected with live Zika virus, demonstrating its efficacy in preventing Zika virus infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Vaccine Based on a Modified Vaccinia Virus Ankara Vector Expressing Zika Virus Structural Proteins Controls Zika Virus Replication in Mice. Pérez, P., Q Marín, M., Lázaro-Frías, A., et al.[2019]

A total of 63 potential T cell epitopes were identified from the Zika virus, with nine promising candidates showing strong binding affinity to various human leukocyte antigen class I supertypes, indicating their potential for generating effective immune responses.

These selected epitopes demonstrated high conservancy across Zika virus strains and minimal similarity to human proteins, suggesting a low risk of autoimmunity, and they could provide over 99% population coverage globally, making them strong candidates for a future Zika vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computational prediction and analysis of potential antigenic CTL epitopes in Zika virus: A first step towards vaccine development. Dikhit, MR., Ansari, MY., Vijaymahantesh, ., et al.[2017]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development. [2021]

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

Vaccine Development for Zika Virus-Timelines and Strategies. [2018]

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

Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Recent Advances in Zika Virus Vaccines. [2023]

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

A Single Dose of NILV-Based Vaccine Provides Rapid and Durable Protection against Zika Virus. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of Zika virus vaccine: A systematic review of clinical trials. [2023]

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

Zika vaccine pre-clinical and clinical data review with perspectives on the future development. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A Vaccine Based on a Modified Vaccinia Virus Ankara Vector Expressing Zika Virus Structural Proteins Controls Zika Virus Replication in Mice. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Computational prediction and analysis of potential antigenic CTL epitopes in Zika virus: A first step towards vaccine development. [2017]