HydroVax-001B Vaccine for West Nile Virus

Not currently recruiting at 1 trial location

Overseen By Sarah L George

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Anticancer drugs, Corticosteroids

Disqualifiers: Flavivirus history, Diabetes, Immunosuppressed, others

Compensation: Varies

Number of Visits: 3

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find a safe and effective vaccine to prevent West Nile virus infection, a disease spread by mosquito bites. Researchers are testing different doses of the HydroVax-001B vaccine to evaluate its efficacy and monitor for any side effects. Participants will receive either the vaccine or a placebo (a harmless inactive substance) and must be healthy adults who have never had a flavivirus infection or vaccine. This study is ideal for those in good health without recent serious medical issues.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you have started a new prescription medication within 30 days of enrollment, it may affect your eligibility unless it's in the same class or a brand/generic switch. Also, certain medications that could pose a risk or interfere with the study might require adjustment.

Is there any evidence suggesting that the HydroVax-001B WNV vaccine is likely to be safe for humans?

Research has shown that the HydroVax-001 vaccine, similar to HydroVax-001B, is safe and well-tolerated in previous studies. These studies reported no serious side effects at the 1 mcg dose, indicating that the vaccine does not cause major side effects at lower doses. The current trial, in its early stages, aims to assess the safety of HydroVax-001B at higher doses of 4 mcg and 10 mcg to ensure it remains safe for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the HydroVax-001B vaccine for West Nile Virus because it introduces a potentially powerful new way to prevent the disease. Unlike current treatments, which primarily focus on managing symptoms or providing supportive care, HydroVax-001B aims to protect against the virus itself through immunization. This vaccine uses a novel formulation that could offer better protection with both low and high dose options. The ability to administer it intramuscularly at specific intervals (Day 1, Day 29, and Day 181) may also enhance its effectiveness and convenience compared to existing options.

What evidence suggests that the HydroVax-001B WNV vaccine might be an effective treatment for West Nile Virus?

Research shows that the HydroVax-001B vaccine for West Nile Virus (WNV) effectively creates a strong immune response. It helps the body produce antibodies that fight infections, particularly effective against certain virus strains. Studies have found that the vaccine is well-tolerated, meaning it does not cause serious side effects. Early results suggest that the vaccine could play a crucial role in preventing WNV infections and reducing related health problems. Overall, these findings indicate that HydroVax-001B is a promising option for protection against West Nile Virus. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Healthy adults aged 18-49 who can follow the study plan and attend all visits. They must consent to blood collection and not be pregnant or breastfeeding. Those with previous flavivirus infections, vaccinations, or likely exposure are excluded.

Inclusion Criteria

Oral temperature is less than 100.4 degrees Fahrenheit at screening

Pulse is 51 to 100 beats per minute, inclusive at screening

Systolic blood pressure is 90 to 140 mmHg, inclusive at screening

Exclusion Criteria

Has history of alcohol or drug abuse within 5 years prior to study vaccination per investigator's discretion

I have diabetes type I or II, or had gestational diabetes that is now resolved.

I have not been hospitalized for psychiatric reasons or posed a danger to myself or others in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the HydroVax-001B WNV vaccine or placebo on Days 1, 29, and 181

26 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for serious adverse events and immunogenicity

13 months

What Are the Treatments Tested in This Trial?

Interventions

• HydroVax-001B WNV

Trial Overview

The trial is testing HydroVax-001B WNV vaccine's safety and ability to provoke an immune response against West Nile Virus in healthy adults compared to a placebo (saltwater). Participants will receive either a low or high dose of the vaccine on specific days.

How Is the Trial Designed?

Group I: Group 1B Experimental Treatment 2 Interventions

A single, high dose, of 10 mcg of HydroVax-001B West Nile Virus (WNV)vaccine administered intramuscularly once on Day 1, Day 29, and Day 181. N=12

Group II: Group 1A Experimental Treatment 2 Interventions

A single, low dose, of 4 mcg of HydroVax-001B West Nile Virus (WNV) vaccine administered intramuscularly once on Day 1, Day 29, and Day 181. N=12

Group III: Group 2A Placebo Group 1 Intervention

A 0.5 mL dose of placebo, consisting of 0.9 % of NaCl, administered intramuscularly once on Day 1, Day 29, Day 181. N=3

Group IV: Group 2B Placebo Group 1 Intervention

A 0.5 mL dose of placebo, consisting of 0.9 % of NaCl, administered intramuscularly once on Day 1, Day 29, Day 181. N=3

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

A novel adenoviral vaccine (CAdVax) was developed that successfully induced both humoral (antibody) and cellular immune responses in mice against West Nile Virus (WNV), suggesting its potential as an effective vaccine.

The vaccine generated broadly neutralizing antibodies against both genetic lineages of WNV, particularly showing strong effectiveness against lineage II, indicating that a multiantigen approach could offer comprehensive protection against various WNV strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex adenovirus-mediated expression of West Nile virus C, PreM, E, and NS1 proteins induces both humoral and cellular immune responses. Schepp-Berglind, J., Luo, M., Wang, D., et al.[2019]

The HydroVax-001WNV vaccine, developed using a hydrogen peroxide-inactivated whole virion approach, showed strong immune responses and protection against West Nile virus in both mice and rhesus macaques, indicating its potential efficacy.

A toxicology study in rats revealed an excellent safety profile for the vaccine, with only minor and temporary irritation at the injection site, and stability tests showed no loss of efficacy over six months under various storage conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine. Poore, EA., Slifka, DK., Raué, HP., et al.[2020]

The WN-VAX vaccine, derived from the West Nile Virus-NY99 strain, demonstrated 100% efficacy in protecting 4-week-old mice from lethal WNV challenges after two doses, even at a very low dilution of 3.2 ng/dose.

Safety tests showed no short- or long-term adverse effects in experimental animals or cell lines, indicating that WN-VAX is safe and ready for planned human trials in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and evaluation of a formalin-inactivated West Nile Virus vaccine (WN-VAX) for a human vaccine candidate. Posadas-Herrera, G., Inoue, S., Fuke, I., et al.[2019]

RepliVAX WN, a vaccine for West Nile virus, has been shown to induce stable antibody responses in hamsters for at least 6 months after vaccination.

Hamsters vaccinated with RepliVAX WN were fully protected from disease when challenged with the virus 6 months later, demonstrating that a single dose can provide long-lasting immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RepliVAX WN, a single-cycle flavivirus vaccine to prevent West Nile disease, elicits durable protective immunity in hamsters. Widman, DG., Ishikawa, T., Winkelmann, ER., et al.[2009]

The HydroVax-001 WNV vaccine, tested in a phase 1 trial with 40 healthy adults, was found to be safe and well-tolerated, with no serious adverse events reported.

At the 4 mcg dose, the vaccine showed modest immunogenicity, with 31% of participants developing neutralizing antibodies, and seroconversion rates increased to 75% when measured by WNV-specific ELISA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults. Woods, CW., Sanchez, AM., Swamy, GK., et al.[2020]

The JE-ADVAX vaccine, which uses an inactivated Japanese encephalitis virus and an adjuvant, provided strong protection against lethal West Nile virus (WNV) challenges in mouse models, even when pre-challenge antibody levels were low.

The vaccine not only increased antibody titers but also generated memory B cells capable of transferring protection to naive mice, highlighting its potential as an alternative approach to combat WNV in the absence of an approved human vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An inactivated cell culture Japanese encephalitis vaccine (JE-ADVAX) formulated with delta inulin adjuvant provides robust heterologous protection against West Nile encephalitis via cross-protective memory B cells and neutralizing antibody. Petrovsky, N., Larena, M., Siddharthan, V., et al.[2021]

RepliVAX WN, a new single-cycle flavivirus vaccine, was found to be safe and effective in a study involving four rhesus macaques, showing strong immune responses after immunization.

After being exposed to the West Nile virus, three out of four vaccinated macaques were completely protected from the virus, while the unvaccinated macaque experienced significant viremia for six days, highlighting the vaccine's protective efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of RepliVAX WN, a single-cycle flavivirus vaccine, in a non-human primate model of West Nile virus infection. Widman, DG., Ishikawa, T., Giavedoni, LD., et al.[2021]

The new HydroVax-II vaccine approach, which combines reduced hydrogen peroxide with copper ions and methisazone, significantly enhances the inactivation of West Nile virus (WNV) while preserving important virus-specific neutralizing epitopes.

This advanced method resulted in a 130-fold increase in WNV-specific neutralizing antibody responses compared to the previous H2O2-only vaccine, providing 100% protection against lethal WNV infection, indicating its potential for effective vaccine development against WNV and other viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine. Quintel, BK., Thomas, A., Poer DeRaad, DE., et al.[2020]

Despite the significant impact of West Nile virus (WNV) in North America, with over 24,000 neurological cases and 2,314 deaths since 1999, there is currently no licensed human vaccine available.

Among the six human vaccine candidates in clinical trials, two live, attenuated vaccines showed strong immunity after a single dose, highlighting the need for further development and research to create an effective vaccine for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty Years of Progress Toward West Nile Virus Vaccine Development. Kaiser, JA., Barrett, ADT.[2023]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06745921

Safety and Immunogenicity of an Inactivated West Nile ...

The secondary objective is to assess immunogenicity of 4 mcg versus 10 mcg dose of HydroVax-001B WNV vaccine given IM on Days 1, 29 and 181 as measured by WNV- ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6640644/

An observer blinded, randomized, placebo-controlled ...

Conclusions. The HydroVax-001 WNV vaccine was found to be modestly immunogenic and welltolerated at all dose levels.

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withpower.com

withpower.com/trial/phase-1-west-nile-viral-infection-11-2024-6976e

HydroVax-001B Vaccine for West Nile Virus

The vaccine generated broadly neutralizing antibodies against both genetic lineages of WNV, particularly showing strong effectiveness against lineage II, ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMp2301816

Combating West Nile Virus Disease — Time to Revisit ...

WNV vaccination would be more effective in preventing WNV disease and related deaths. Lessons from the development of other vaccines can be ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0264410X16311513

Pre-clinical development of a hydrogen peroxide ...

Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001 WNV is a promising vaccine candidate.

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0264410X18316992

Vaccine

HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not ...

7.

idcrc.org

idcrc.org/about/news-archive/west-nile.html

IDCRC launches clinical trail to study the safety and ...

This trial will assess the safety and immunogenicity of the second-generation HydroVax-001B WNV vaccine, produced by Najit Techonolgies, Inc., ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6816401/

West Nile virus vaccines – current situation and future directions

Firstly, two doses of a hydrogen peroxide inactivated WNV vaccine led to detectable neutralizing antibodies in approx. 50% of the study participants. The ...

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scholars.duke.edu

scholars.duke.edu/individual/pub1367022

An observer blinded, randomized, placebo-controlled, phase I ...

RESULTS: HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not ...