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.
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.
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.
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.
- 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