HydroVax-001B Vaccine for West Nile Virus

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

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the HydroVax-001B WNV treatment for West Nile Virus?

Research shows that the HydroVax-001WNV vaccine, which is similar to HydroVax-001B, produced strong immune responses and protected animals from West Nile Virus in pre-clinical studies. Additionally, a new version of this vaccine approach resulted in significantly higher antibody responses and complete protection against the virus in animal models. ^{1 2 3 4 5}

Is the HydroVax-001B Vaccine for West Nile Virus safe for humans?

Pre-clinical studies of HydroVax-001WNV, a similar vaccine, showed an excellent safety profile in animals, with only minor and temporary irritation at the injection site. ^{1 2 3 6 7}

How is the HydroVax-001B WNV treatment different from other treatments for West Nile Virus?

HydroVax-001B WNV is unique because it uses a hydrogen peroxide-based method to inactivate the virus, which helps maintain the virus's structure to trigger a strong immune response. This approach is different from other treatments as it combines hydrogen peroxide with copper ions and methisazone, enhancing the vaccine's ability to produce protective antibodies. ^{1 2 5 8 9}

What is the purpose of this trial?

A randomized, placebo controlled, double-blind (within dosing group), sequential dose escalation study. This phase 1 trial addresses the urgent need for a vaccine to prevent disease resulting from infection with West Nile virus (WNV), a virus that is primarily spread to people by the bite of an infected mosquito. The purpose of this Phase 1 trial is to evaluate the safety and immunogenicity of the HydroVax-001B WNV vaccine in healthy adult volunteers. The study Population will consist of healthy male and non-pregnant, non-breastfeeding female adults, 18 to 49 years of age, inclusive. Potential participants with a history of prior flavivirus infection or receipt of any flavivirus vaccine or monoclonal antibody, and those who likely had a prior flavivirus infection based on exposure history will be ineligible for the study. Participants will be randomized to receive HydroVax-001B WNV vaccine or placebo in a 12:3 ratio within a dosage group. Participants will be sequentially enrolled into two dosage groups. The primary objective is to assess the safety and reactogenicity of 4 mcg versus 10 mcg dose of the HydroVax-001B WNV vaccine administered intramuscularly (IM) on Days 1, 29 and 181.

Eligibility Criteria

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine. [2020]

2. Netherlands 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. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Twenty Years of Progress Toward West Nile Virus Vaccine Development. [2023]

4. United States 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. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Development and evaluation of a formalin-inactivated West Nile Virus vaccine (WN-VAX) for a human vaccine candidate. [2019]

7. United States 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. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

RepliVAX WN, a single-cycle flavivirus vaccine to prevent West Nile disease, elicits durable protective immunity in hamsters. [2009]

9. United States 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. [2019]