SBIR-STTR Award

A Randomized Phase I Clinical Trial of HydroVax-YFV, a Novel Inativated Yellow Fever Vaccine
Profile last edited on: 5/25/2022

Program
SBIR
Agency
NIH | NIAID
Total Award Amount
$1,291,792
Award Phase
2
Principal Investigator
Ian J Amanna
Activity Indicator

Company Information

Najit Technologies Inc

15232 NW Greenbrier Parkway
Beaverton, OR 97006
   (971) 727-3571
   info@najittech.com
   www.najittech.com
Multiple Locations:   
Congressional District:   01
County:   Washington

Phase I

Phase I year
2019
Phase I Amount
$292,140
Yellow fever virus (YFV) is a mosquito-borne emerging/re-emerging hemorrhagic fever virus that causes 20- 60% mortality and is endemic in >40 countries. The current live attenuated YFV vaccine was developed in 1936 and has proven to be effective at saving millions of lives from this devastating disease. Nevertheless, this is a live-attenuated vaccine that is contraindicated in healthy people who have egg allergies as well as vulnerable populations including young infants, pregnant or breastfeeding women, and the elderly. During recent outbreaks, these at-risk groups have had no alternatives to live yellow fever vaccination and our goal is to produce a vaccine that is safe for both healthy and vulnerable populations. According to the CDC, live YFV vaccines cause 47 serious adverse events (SAE) per million vaccinations (SAE defined as resulting in hospitalization, long-term disability, or death). Vaccine-associated neurological disease occurs at a rate of up to 1 case per 10,000 vaccinations. YFV vaccination of infants <9 months of age has been contraindicated since the 1960’s due to excessively high rates of vaccine-associated encephalitis in this age group. More recently, live YFV vaccination has been contraindicated in breastfeeding mothers due to documented cases of virus transmission via breastmilk to infants who later developed YFV-associated neurological disease including seizures. In patients >60 years of age, YFV vaccination causes severe viscerotropic disease at an incidence rate of approximately 1:50,000 with a mortality rate of >50%. The overall mortality rate following YFV vaccination (all ages) is estimated at 1 to 2 deaths per million doses. Despite these clear gaps in vaccination coverage, there is currently no commercial vaccine available for these vulnerable populations. To address this critical unmet need, we have discovered a safe and immunogenic peroxide-inactivated yellow fever vaccine, HydroVax-YFV. Importantly, this advanced vaccine is safe and provides complete protection against lethal viscerotropic yellow fever in a robust non-human primate model. Here, we propose a double-blind, randomized, placebo-controlled Phase I dose escalation trial to evaluate the preliminary safety and immunogenicity of HydroVax-YFV. Our goal is to eventually expand vaccine coverage to a broader range of patients and the successful completion of this study will represent a key milestone in the advancement of a clinically relevant vaccine against yellow fever and provide a much-needed approach to protect the most susceptible members of society including infants, elderly, and those with potentially compromised immune functions.

Public Health Relevance Statement:
In this proposal, we provide preclinical data demonstrating the safety, immunogenicity, and protective efficacy of an advanced HydroVax vaccine platform and propose to evaluate the safety and immunogenicity of a novel peroxide-inactivated whole-virus yellow fever vaccine in a double-blind placebo-controlled Phase I clinical trial.

Project Terms:
Acute; Address; Adult; Adverse event; Age; age group; Age-Months; Age-Years; Allergy to eggs; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; Award; base; Breast Feeding; burden of illness; Case Fatality Rates; Centers for Disease Control and Prevention (U.S.); Cessation of life; cGMP production; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; clinically relevant; Country; Data; Data Analyses; Development; disability; Disease; Disease Outbreaks; Dose; Double-Blind Method; Ebola virus; Elderly; Encephalitis; Enrollment; FDA approved; Female; Fever; Flavivirus; Goals; Grant; Hemorrhage; hemorrhagic fever virus; Hepatitis; Hospitalization; Human Milk; Hydrogen Peroxide; immune function; Immunization; immunogenic; immunogenicity; Incidence; Individual; Infant; Infrastructure; Institutes; Investigational Drugs; Investigational New Drug Application; Kidney Failure; Laboratories; male; man; Medical; member; Modeling; mortality; mosquito-borne; mosquito-borne pathogen; Mothers; National Institute of Allergy and Infectious Disease; Nausea and Vomiting; nervous system disorder; nonhuman primate; novel; nursing mothers; Outcome Measure; Package Insert; Patients; Peroxides; Phase; Phase I and II Vaccine Trials; Phase I Clinical Trials; phase I trial; Placebos; pre-clinical; pregnant; Pregnant Women; Prevention; primary endpoint; Production; protective efficacy; Protocols documentation; Randomized; Reporting; Research Personnel; Risk; Safety; safety assessment; Savings; secondary endpoint; Seizures; Serious Adverse Event; seroconversion; Signs and Symptoms; Societies; stability testing; Technology; Test Result; Testing; Time; Toxic effect; Toxicology; United States National Institutes of Health; Vaccination; vaccine candidate; vaccine development; vaccine trial; Vaccines; Veterans; viral transmission; Virus; Vulnerable Populations; West Nile virus; Woman; Wood material; Yellow Fever; Yellow Fever Vaccine; Yellow fever virus

Phase II

Phase II year
2021 (last award dollars: 2021)
Phase II Amount
$999,652
Yellow fever virus (YFV) is a mosquito-borne emerging/re-emerging hemorrhagic fever virus that causes 20- 60% mortality and is endemic in >40 countries. The current live attenuated YFV vaccine was developed in 1936 and has proven to be effective at saving millions of lives from this devastating disease. Nevertheless, this is a live-attenuated vaccine that is contraindicated in healthy people who have egg allergies as well as vulnerable populations including young infants, pregnant or breastfeeding women, and the elderly. During recent outbreaks, these at-risk groups have had no alternatives to live yellow fever vaccination and our goal is to produce a vaccine that is safe for both healthy and vulnerable populations. According to the CDC, live YFV vaccines cause 47 serious adverse events (SAE) per million vaccinations (SAE defined as resulting in hospitalization, long-term disability, or death). Vaccine-associated neurological disease occurs at a rate of up to 1 case per 10,000 vaccinations. YFV vaccination of infants <9 months of age has been contraindicated since the 1960's due to excessively high rates of vaccine-associated encephalitis in this age group. More recently, live YFV vaccination has been contraindicated in breastfeeding mothers due to documented cases of virus transmission via breastmilk to infants who later developed YFV-associated neurological disease including seizures. In patients >60 years of age, YFV vaccination causes severe viscerotropic disease at an incidence rate of approximately 1:50,000 with a mortality rate of >50%. The overall mortality rate following YFV vaccination (all ages) is estimated at 1 to 2 deaths per million doses. Despite these clear gaps in vaccination coverage, there is currently no commercial vaccine available for these vulnerable populations. To address this critical unmet need, we have discovered a safe and immunogenic peroxide-inactivated yellow fever vaccine, HydroVax-YFV. Importantly, this advanced vaccine is safe and provides complete protection against lethal viscerotropic yellow fever in a robust non-human primate model. Here, we propose a double-blind, randomized, placebo-controlled Phase I dose escalation trial to evaluate the preliminary safety and immunogenicity of HydroVax-YFV. Our goal is to eventually expand vaccine coverage to a broader range of patients and the successful completion of this study will represent a key milestone in the advancement of a clinically relevant vaccine against yellow fever and provide a much-needed approach to protect the most susceptible members of society including infants, elderly, and those with potentially compromised immune functions.

Public Health Relevance Statement:


Public Health Relevance:
In this proposal, we provide preclinical data demonstrating the safety, immunogenicity, and protective efficacy of an advanced HydroVax vaccine platform and propose to evaluate the safety and immunogenicity of a novel peroxide-inactivated whole-virus yellow fever vaccine in a double-blind placebo-controlled Phase I clinical trial.

Project Terms:
<21+ years old>