Flagellin/F1/V Vaccine: Novel Flagellin-based Vaccine Against Pneumonic Plague

Flagellin/F1/V is a flagellin-based vaccine that has demonstrated high effectiveness against pneumonic plague in primate and rodent models. The vaccine also induced the production of extraordinarily high levels of protective response in two non-human primate species. In studies, the vaccine induced significant and dose dependent production of antibodies against plague antigens in test subjects. This vaccine could be widely used to protect both military and civilian populations against outbreaks or attacks of pneumonic plague.

Problem

Pneumonic plague is a rapidly progressing respiratory form of plague caused by the bacterium Yersinia pestis. Nearly 100 percent of untreated pneumonic plague infections result in death. Currently, there is no effective protection against pneumonic plague . The World Health Organization has reported sporadic outbreaks in Africa, Asia, and South America. The FDA-approved plague vaccine currently available is an inactivated vaccine that has questionable effectiveness against pneumonic plague and causes significant side effects such as malaise, fever, headache and swollen lymph glands. 

Solution

Researchers have designed a novel flagellin-based fusion protein vaccine with a highly potent and long-lasting immunity and an acceptable safety profile. In a human phase I study conducted by NIH/NIAID, there was a dose-dependent immune response to F1 and V antigens of the Y. pestis organism as well as flagellin adjuvant. Importantly, in comparison to the existing vaccine, no severe adverse reactions were noted in a Phase I clinical trial.

Competitive Benefits

  • Potential to be the first FDA-approved vaccine specifically useful for pneumonic plague
  • Vaccine effective at low doses with acceptable side effect profile
  • Can be administered either intranasally or intramuscularly
  • Cost-effective, low dose formulations due to flagellin-based design
  • Long shelf life – over 10 months at 4°C and 28 days at 37oC

Inventors

  • Steven B. Mizel, PhD, Department of Microbiology and Immunology, Wake Forest School of Medicine
  • Anna N. Honko, PhD, United States Army Medical Research Institute of Infectious Diseases

Application Fields

Pneumonic plague, military personnel, civilian populations, bioterrorism protection, laboratory and field personnel exposed to Y. pestis.

Stage of Development

An Investigation New Drug Application (IND) is on file with the FDA and a human Phase I clinical trial has been completed. Phase I results indicate the vaccine is safe and tolerated up to a 10 mcg dose. Next development step includes a human Phase 1b trial to increase dose range to 30 mcg. 

Publication

Mizel, SB et al. Flagellin-F1-V Fusion Protein is an Effective Plague Vaccine in Mice and Two Species of Nonhuman Primates. Clin. Vaccine Immunol. 2009:16(1)21-8

Patents

  • U.S. patent: 7,794,731,8,198,424
  • Foreign patents: EPO 1827489, AU 2005316265, JP 5094407

Keywords

Plague, Yersinia pestis, epidemic, bioterrorism, flagellin, fusion protein vaccines

Licensing Contact

Peter Golikov, MBA
Licensing Director
Center for Technology Innovation & Commercialization
Wake Forest Innovations
pgolikov@wakehealth.edu
+1.336.713.1664

Reference #: 05-13

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