Vaccine for Zika
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: Valneva Austria GmbH
Stay on Your Current Meds
No Placebo Group
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 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.
12345What 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.
12367Eligibility 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
+2 more
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
+13 more
Participant Groups
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.
5Treatment groups
Experimental Treatment
Group I: VLA1601 Medium doseExperimental Treatment1 Intervention
Group II: VLA1601 Low dose + CpG 1018®Experimental Treatment2 Interventions
Group III: VLA1601 Low dose + 3M-052-AFExperimental Treatment2 Interventions
Group IV: VLA1601 Low doseExperimental Treatment1 Intervention
Group V: VLA1601 High doseExperimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Velocity Clinical ResearchSioux City, IA
Velocity Clinical ResearchLincoln, NE
Flourish ResearchChicago, IL
Velocity Clinical ResearchOmaha, NE
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Who Is Running the Clinical Trial?
Valneva Austria GmbHLead Sponsor
References
A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development. [2021]The emergence and rapid spread of Zika virus (ZIKV) on a global scale as well as the establishment of a causal link between Zika infection and congenital syndrome and neurological disorders triggered unprecedented efforts towards the development of a safe and effective Zika vaccine. Multiple vaccine platforms, including purified inactivated virus, nucleic acid vaccines, live-attenuated vaccines, and viral-vectored vaccines, have advanced to human clinical trials. In this review, we discuss the recent advances in the field of Zika vaccine development and the challenges for future clinical efficacy trials. We provide a brief overview on Zika vaccine platforms in the pipeline before summarizing the vaccine candidates in clinical trials, with a focus on recent, promising results from vaccine candidates that completed phase I trials. Despite low levels of transmission during recent years, ZIKV has become endemic in the Americas and the potential of large Zika outbreaks remains real. It is important for vaccine developers to continue developing their Zika vaccines, so that a potential vaccine is ready for deployment and clinical efficacy trials when the next ZIKV outbreak occurs.
Vaccine Development for Zika Virus-Timelines and Strategies. [2018]Zika virus is a mosquito-borne Flavivirus that spread rapidly through South and Central America in 2015 to 2016. Microcephaly has been causally associated with Zika virus infection during pregnancy and the World Health Organization declared Zika virus as a Public Health Emergency of International Concern. To address this crisis, many groups have expressed their commitment to developing a Zika virus vaccine. Different strategies for Zika virus vaccine development are being considered including recombinant live attenuated vaccines, purified inactivated vaccines (PIVs), DNA vaccines, and viral vectored vaccines. Important to Zika virus vaccine development will be the target group chosen for vaccination and which end point(s) is chosen for efficacy determination. The first clinical trials of Zika virus vaccine candidates will begin in Q3/4 2016 but the pathway to licensure for a Zika virus vaccine is expected to take several years. Efforts are ongoing to accelerate Zika virus vaccine development and evaluation with the ultimate goal of reducing time to licensure.
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]The development of an effective vaccine against Zika virus remains a public health priority. A Zika purified inactivated virus (ZPIV) vaccine candidate has been shown to protect animals against Zika virus challenge and to be well tolerated and immunogenic in humans up to 8 weeks of follow-up. We aimed to assess the safety and immunogenicity of ZPIV in humans up to 52 weeks of follow-up when given via standard or accelerated vaccination schedules.
Recent Advances in Zika Virus Vaccines. [2023]The recent outbreaks of Zika virus (ZIKV) infections and associated microcephaly in newborns has resulted in an unprecedented effort by researchers to target this virus. Significant advances have been made in developing vaccine candidates, treatment strategies and diagnostic assays in a relatively short period of time. Being a preventable disease, the first line of defense against ZIKV would be to vaccinate the highly susceptible target population, especially pregnant women. Along those lines, several vaccine candidates including purified inactivated virus (PIV), live attenuated virus (LAV), virus like particles (VLP), DNA, modified RNA, viral vectors and subunit vaccines have been in the pipeline with several advancing to clinical trials. As the primary objective of Zika vaccination is the prevention of vertical transmission of the virus to the unborn fetus, the safety and efficacy requirements for this vaccine remain unique when compared to other diseases. This review will discuss these recent advances in the field of Zika vaccine development.
A Single Dose of NILV-Based Vaccine Provides Rapid and Durable Protection against Zika Virus. [2021]Zika virus, a member of the Flaviviridae family, is primarily transmitted by infected Aedes species mosquitoes. In 2016, Zika infection emerged as a global health emergency for its explosive spread and the remarkable neurological defects in the developing fetus. Development of a safe and effective Zika vaccine remains a high priority owing to the risk of re-emergence and limited understanding of Zika virus epidemiology. We engineered a non-integrating lentiviralvector(NILV)-based Zika vaccine encoding the consensus pre-membrane and envelope glycoprotein of circulating Zika virus strains. We further evaluated the immunogenicity and protective efficacy of this vaccine in both immunocompromised and immunocompetent mouse models. A single immunization in both mouse models elicited a robust neutralizing antibody titer and afforded full protection against Zika challenge as early as 7 days post-immunization. This NILV-based vaccine also induced a long-lasting immunity when immunized mice were challenged 6 months after immunization. Altogether, our NILV Zika vaccine provides a rapid yet durable protection through a single dose of immunization without extra adjuvant formulation. Our data suggest a promising Zika vaccine candidate for an emergency situation, and demonstrate the capacity of lentiviral vector as an efficient vaccine delivery platform.
Safety and immunogenicity of Zika virus vaccine: A systematic review of clinical trials. [2023]Several phase-1 clinical trials have been performed to evaluate the safety and efficacy of candidate anti-Zika vaccines. In this systematic review, we systematically evaluated the safety and immunogenicity of candidate vaccines, which would aid researchers in formulating an effective vaccination strategy for phase-2 trials based on current evidence. A literature search was conducted using the electronic databases MEDLINE through Pubmed, Web of Science, and Cochrane Database for relevant studies on candidate anti-zika vaccines. Studies on animal models were excluded from our study. Healthy individuals who were administered candidate Zika vaccines to evaluate the immune response and adverse events (AEs) compared to placebo were considered. Data were extracted, tabulated, and analysed using Microsoft Excel, while the risk of bias plots were generated using tidyverse and Robvis packages in R-studio. A total of five phase-1 clinical trials were included in our analysis comprising of studies on inactivated, viral vector, and DNA vaccines. Immunogenicity ranged from 10% to 100% after vaccination with the lowest seroconversion rate (10%) and geometric mean titre (GMT) (6.3; 95% confidence interval (CI):3.7-10.8) observed among recipients of single-dose inactivated anti-zika vaccine (ZPIV). For DNA vaccines, the seroconversion rate ranged from 60% to 100% with the highest seroconversion rate (100%) and GMT (2871; 95% CI:705.3-11688) observed among recipients of three shots of high dose GLS-5700 vaccine. For viral vector vaccine (Ad26.ZIKV.001) seroconversion rate (100%) and GMT peaked after two shots with both low and high-dose vaccines. In all those studies AEs were mostly local including injection site pain, erythema, and itching. The most common systemic AEs included fever, myalgia, nausea, and fatigue. In phase-1 clinical trials, all candidate vaccines were found to be highly immunogenic and relatively safe, especially when administered in higher doses and with the help of needle-free devices.
Zika vaccine pre-clinical and clinical data review with perspectives on the future development. [2023]Zika is an arboviral illness caused by infection with the Zika flavivirus. Transmission most commonly occurs during a feeding event involving an infected Aedes mosquito or vertical transmission between an infected mother to her fetus. Infection outcomes range from asymptomatic to devastating neurologic injuries in children infected in utero. The recognition of Congenital Zika Syndrome prompted the declaration of an international health emergency and a call to rapidly develop medical countermeasures such as vaccines and therapeutics. A flurry of research and development activity in industry, government, non-governmental organizations, and academia during the most recent Zika epidemic (2015) stimulated the development of a number of vaccine candidate prototypes, generation of pre-clinical data, and the conduct of early phase human trials. The safety and immunogenicity of different vaccine platforms were demonstrated and mouse and non-human primate passive transfer studies hinted at the potential for clinical benefit in humans and defining an immune correlate of protection. A rapid decline in regional transmission, however, prevented the conduct a clinical endpoint efficacy trial. The pathway to licensure of a Zika vaccine remains unclear.
A Vaccine Based on a Modified Vaccinia Virus Ankara Vector Expressing Zika Virus Structural Proteins Controls Zika Virus Replication in Mice. [2019]Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that affects humans and can cause severe neurological complications, including Guillain-Barré syndrome and microcephaly. Since 2007 there have been three large outbreaks; the last and larger spread in the Americas in 2015. Actually, ZIKV is circulating in the Americas, Southeast Asia, and the Pacific Islands, and represents a potential pandemic threat. Given the rapid ZIKV dissemination and the severe neurological and teratogenic sequelae associated with ZIKV infection, the development of a safe and efficacious vaccine is critical. In this study, we have developed and characterized the immunogenicity and efficacy of a novel ZIKV vaccine based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the ZIKV prM and E structural genes (termed MVA-ZIKV). MVA-ZIKV expressed efficiently the ZIKV structural proteins, assembled in virus-like particles (VLPs) and was genetically stable upon nine passages in cell culture. Immunization of mice with MVA-ZIKV elicited antibodies that were able to neutralize ZIKV and induced potent and polyfunctional ZIKV-specific CD8+ T cell responses that were mainly of an effector memory phenotype. Moreover, a single dose of MVA-ZIKV reduced significantly the viremia in susceptible immunocompromised mice challenged with live ZIKV. These findings support the use of MVA-ZIKV as a potential vaccine against ZIKV.
Computational prediction and analysis of potential antigenic CTL epitopes in Zika virus: A first step towards vaccine development. [2017]The Zika virus disease is an Aedes mosquito-borne disease caused by the ZIKA virus. The unavailability of vaccines or proper chemotherapeutic treatment emphasizes the need for the development of preventive and therapeutic vaccines. T cell specific epitopes have been used as vaccine candidates to generate desired immune responses against a variety of viral pathogens. Herein, the immune-informatics approach was used for the screening of potential major histocompatibility complex class I restricted epitopes, which may be competent to generate a cell-mediated immune response in humans. A total of 63 epitopes were identified, which revealed a comprehensive binding affinity to the 42 different human leukocyte antigen class I supertypes: A01, A02, A08, A23, A24, A25, A26, A29, A30, A32, A66, A68, A69, A80, B07, B08, B14, B15, B27, B35, B39, B40, B42, B45, B46, B48, B51, B53, B54, B57, B58, B83, C12, C03, C04, C05, C06, C07, C08, C12, C14, and C15, and which had no homologs in humans. By combining the human leukocyte antigen binding specificity and population coverage, nine promiscuous epitopes located in Capsid 1 Protein (MVLAILAFL(P1)), Envelop Protein (RLKGVSYSL (P2) and RLITANPVI (P3)), NS2A (AILAALTPL (P4)), NS4B (LLVAHYMYL (P5) and LVAHYMYLI (P6)) and NS5 (SLINGVVRL (P7), ALNTFTNLV (P8) and YLSTQVRYL (P9)) were shortlisted. Most of these consensus epitopes revealed 100% conservancy in all Zika virus strains and were very less conserved against the human proteome. The combination of the selected epitopes accounted for an optimal coverage in the world wide population (>99%) independent of ethnicity. Structural analysis of these selected epitopes by the PatchDock web server showed their preferential mode of presentation to the T cell receptor. All these results recommended the possibility of a combined epitope vaccine strategy and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates.