Researchers at Wake Forest School of Medicine have developed, manufactured and tested a number of new vaccines predicated on a platform of flagellin as an adjuvant and carrier of a range of protein antigens. Flagellin fusion protein vaccines against plague, Pseudomonas aeruginosa, drugs of abuse/addiction, cancer and pneumococcus efficiently elicit significant protective immune responses in animal models and are simple to make using recombinant DNA techniques. The new approach of using the proven adjuvant flagellin as an antigen carrier provides highly potent and cost-effective vaccines and a versatile platform to develop multiple preventive and therapeutic vaccines.
Although pneumonic plague is a rapidly progressing disease with a mortality rate approaching 100 percent, there is no licensed vaccine for plague that is effective against the pneumonic form of the disease. Researchers have created a novel vaccine using a fusion protein that comprises flagellin and the F1- and V-antigens of Yersinia pestis. The vaccine results in powerful immunity against pneumonic plague in mice and non-human primates.
- In Phase 1 clinical trial
- Potential to be the first approved vaccine for pneumonic plague
- Vaccine is equally effective when given intranasally or intramuscularly to non-human primates and does not elicit any adverse reactions, providing multiple safe routes of administration
- Vaccine elicits sterile immunity in mice challenged with Y. pestis, i.e. the vaccine promotes complete bacterial clearance
- Vaccine is dramatically more potent than other plague vaccines, i.e. less vaccine is required to elicit a protective immune response, resulting in cost-effective treatment and production
- GMP manufactured vaccine has a stability of more than 10 months at 4 deg C, providing a shelf-stable vaccine
- Issued U.S. patent 7,794,731
- Immunization of military personnel in high-risk areas
- Immunization of civilian populations to prevent an epidemic of pneumonic plague
- Bioterrorism protection against pneumonic plague used as a biological weapon
Steven B. Mizel, PhD
Anna N. Honko, PhD (U.S. Army Medical Research)
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
Other Flagellin-based Vaccines
Pseudomonas Aeruginosa Vaccine
There is currently no approved vaccine for P. aeruginosa, a major cause of morbidity and mortality in cystic fibrosis patients and ventilated patients (>$1.5B market). Researchers have developed a vaccine that produces a robust immune response using a fusion protein of flagellin and the OprI and OprF antigens.
- Vaccine produces a protective immune response in young African green monkeys and a dramatically enhanced P. aeruginosa clearance in mice with no lung damage
- Multivalency of the vaccine creates a synergistic effect, giving an improved immunogenic response and better vaccine coverage compared to other P. aeruginosa vaccines in development
- Vaccine is highly potent, resulting in efficacious low-dose vaccine formulations that are cost-effective to produce
- Patent pending
Drugs of Abuse Vaccine
Vaccine therapy has emerged as a promising tool for combating drug abuse (>$1B market). Current strategies require a large number of immunizations, large amounts of material and result in rapid decline in antibody titers. A vaccine comprised of a drug-flagellin conjugate may promote long-lasting, high levels of antibody production with small amounts of material because of the powerful adjuvant activity of flagellin.
- Flagellin-cocaine conjugate vaccine has been constructed and is being tested in vivo
- Patent pending
Although the cancer vaccine market (>$500M) is growing, an efficient treatment strategy does not exist for many types of cancers. Researchers have developed a flagellin-based vaccine technology that may provide a preventive or treatment option for many of these cancers.
- Breast cancer vaccine, consisting of a fusion protein of flagellin and the Fra-1 antigen, elicits reduced tumor growth in mice
- Vaccine is selective for breast cancer cells and non-invasive, as compared to standard therapy such as surgery, radiation and chemotherapy, which may lead to safer cancer treatment strategies
- Any cancer antigen can be incorporated into the flagellin fusion protein, giving prospects of developing various cancer vaccine treatments and having a substantial market share
- Ongoing research at Wake Forest School of Medicine is examining the effect of incorporating other cancer antigens into the fusion protein vaccine
- Patent pending
The incidence of pneumococcal disease is on the rise, as current vaccines do not adequately protect against pneumococcal serotypes causing the disease (Market >$3B). Available vaccines fail to cover 10 percent to 15 percent of the pneumococcal serotypes responsible for pneumococcal disease, and as a result, an estimated 175,000 patients are hospitalized with pneumonia each year in the U.S. alone. Researchers have created a pneumococcal vaccine consisting of a fusion protein of flagellin and various pspA antigens that is likely to have greater breadth of protection than the existing vaccines, resulting in better prevention of disease. Currently, the vaccine has been observed to induce a robust immune response in mice. Patent pending.
Michael Batalia, PhD
Executive Director, Commercialization