NIH-sponsored Phase 1 clinical trial evaluates novel investigational West Nile virus vaccine

A novel investigational West Nile virus vaccine discovered and developed by scientists at the Oregon National Primate Research Center at Oregon Health & Science University is being evaluated in an NIH-sponsored Phase 1, first-in-human, clinical trial at Duke University. Although several early-stage West Nile virus vaccine clinical trials have been completed to date, no human vaccine has been approved for commercial use.

"West Nile virus represents a significant threat to public health in the United States, especially among the immunocompromised and the elderly," said Mark Slifka, Ph.D., professor of molecular microbiology and immunology in the OHSU School of Medicine; senior scientist at the Oregon National Primate Research Center at OHSU; and president and chief scientific officer of Najit Technologies, Inc. "We believe our vaccine approach will not only be safe and effective for West Nile virus, but it could also provide significant protection against other important human pathogens, including yellow fever, dengue hemorrhagic fever, and, potentially even Ebola."

OHSU's investigational West Nile virus vaccine candidate was created using a proprietary, peroxide-based platform called HydroVax™. The platform is unique in that it is the first vaccine production system to demonstrate that hydrogen peroxide can inactivate viruses for use as vaccines while still maintaining key immunogenic, or immune-system triggering, structures. Older vaccine production systems use formaldehyde-fixed 'dead' forms of the virus, but this often results in substantial damage to the native surface structures of the virus.

To develop a clinical-grade West Nile virus vaccine for the Phase I clinical trial, Slifka and colleagues worked with Michael Diamond, M.D., Ph.D., a world-renowned expert on West Nile virus immunology and pathogenesis at Washington University in St. Louis, and Ian Amanna, Ph.D., associate vice president for research at Najit Technologies, Inc., an Oregon-based OHSU spinoff company that serves as the researchers' industry partner.

"The generation of a safe and effective inactivated vaccine against West Nile virus could minimize disease, long-term disability and even death in vulnerable individuals," said Diamond. "This vaccine showed great promise in pre-clinical models in animals. We are optimistic that it will stimulate protective immune responses that control infection and disease. This first trial in humans is an important milestone."

In 2009, Slifka, Diamond, Amanna and colleagues received a $7.5 million grant from the National Institutes of Health to develop a new West Nile Vaccine. In 2012, using a mouse model, the researchers proved their proprietary HydroVax platform was a safer and more effective method for creating vaccines than current vaccine production systems (Nature Medicine). In 2013, the Diamond laboratory showed that HydroVax could protect aged mice from lethal West Nile virus infection (Journal of Virology). Last month, an independent group of researchers led by Yoshiro Kawaoka, Ph.D., at the University of Wisconsin used HydroVax to develop an Ebola vaccine that provided complete protection against lethal infection in a primate model (Science).

"Development of this vaccine platform has truly been a team effort. We had virologists, immunologists, and vaccinologists all working together with regulatory consultants and manufacturing experts. When coupled with substantial input by the NIH and the FDA, we were able to develop this exciting new vaccine candidate for West Nile virus," said Slifka.

West Nile virus is a mosquito-borne human pathogen that has become endemic in North America and causes substantial disease and death. Some estimate that as many as 3 million West Nile virus infections have occurred in the United States since 1999. A total of 47 states and the District of Columbia reported West Nile virus infections in people, birds or mosquitoes in 2014, according to the Centers for Disease Control and Prevention.

"It is truly gratifying to see this novel approach to vaccine development discovered by Dr. Slifka and his colleagues take this critical step toward treatment of infectious diseases in humans," said Dan Dorsa, Ph.D., senior vice president for research at OHSU.