Oregon Health and Science University said this week that it will collaborate with OHSU spinout Najit Technologies and Washington University in St. Louis to develop a vaccine for West Nile virus under a four-year, $7.3 million grant from the National Institute of Allergy and Infectious Diseases.
The partners, using a platform technology owned by OHSU and exclusively licensed to Najit, plan to create an inactivated formulation that remains highly immunogenic but may be safer to administer to immunocompromised patients than existing vaccines.
As such, OHSU stands to benefit financially if Najit can successfully market a vaccine for West Nile virus, or for any other infectious disease. Najit said that it may explore using the platform to develop vaccines for related flaviviruses and even influenza.
"We have a platform technology, and we can essentially plug and play by putting new diseases into the system," Mark Slifka, principal investigator on the NIAID grant, told BTW this week.
Najit, which Slifka founded in 2004 to develop diagnostic assays and vaccines for infectious diseases that primarily affect developing countries, will produce a clinical-grade version of the vaccine and shepherd it through Phase I clinical trials.
Slifka, who is president and CSO of Najit as well as an associate scientist at OHSU's Vaccine and Gene Therapy Institute in Portland, said that although Najit was founded with an eye toward diagnostics and vaccine development, with the latest grant it will "really start to focus more on vaccine development."
OHSU and Najit will work with the laboratory of Michael Diamond, an expert on West Nile virus immunology at Washington University School of Medicine. Diamond is a co-PI on the grant, Slifka said, but his institution's involvement is purely academic in that it was not involved with the invention of the vaccine-manufacturing platform technology.
"They're more interested in the fundamental aspects of vaccine development in animal models," Slifka said. However, he noted that it is possible that new IP could arise from the partnership, and that OHSU and WUSM would address ownership of new inventions on a case-by-case basis.
H2O2 to the Rescue
OHSU stands to benefit financially if Najit can market the vaccine. In August 2006, the school filed a patent application in the US that supports the vaccine technology at the heart of the partnership.
In 2007, OHSU gave Najit exclusive rights to the technology in exchange for an undisclosed equity stake in the company and undisclosed royalties on future product sales.
"As a small company, we wouldn’t have the money to buy an exclusive license agreement straight out, so for us, giving the university an equity position made the most sense," Slifka said.
The patent application, entitled "Inactivating pathogens with hydrogen peroxide for vaccine production," is based on the theory that human cells infected with a virus produce hydrogen peroxide, which inactivates the pathogen but doesn't necessarily destroy it completely.
The OHSU/Najit vaccine-development method, called Hydrovax, uses hydrogen peroxide to inactivate the pathogen, instead of the more-widely used formaldehyde, which can be overly destructive and therefore dilute vaccine potency.
Initial research from Slifka's lab indicates that peroxide-based vaccines may induce a 10-fold greater immune response compared with natural infection, and that it should remain safe in particularly susceptible populations, such as young children, the elderly, and those with compromised immune systems. Preliminary studies have also shown that the vaccine protects mice against lethal West Nile infection.
And because of the platform nature of the technology, Najit said that it may use it to explore vaccine development for other infectious diseases. It would be easiest if those diseases were related viruses such as Dengue fever, yellow fever, and Japanese encephalitis virus, but the platform might also prove beneficial for creating safer vaccines for more common infections, such as influenza, Slifka said.
But first, the partners will collaborate to develop a vaccine specifically for West Nile virus, which they call "a significant threat to public health in the US," particularly in vulnerable populations.
"Although most WNV infections are either mild or asymptomatic, neuroinvasive disease is accompanied by a high mortality rate – up to 35 percent in the hospitalized elderly," Slifka wrote in the grant abstract. "Moreover, up to 77 percent of survivors who recover from acute WNV encephalitis endure long-term neurological sequelae resulting in problems such as impaired gait, muscle weakness, hearing loss, and tremors" for as long as three years following infection.
Although a veterinary vaccine currently exists for the mosquito-borne pathogen, there are currently no US Food and Drug Administration-approved vaccines for preventing the infection in humans.
Meantime, the virus has in recent years spread throughout most of the Americas and the Caribbean, and its occurrence has proliferated.
According to the US Centers for Disease Control, in 1999 there were 62 reported cases of West Nile virus in the US resulting in seven deaths, with New York being the only state to report incidence. In 2007, there were 3,630 confirmed cases of the disease resulting in 124 deaths across 42 US states.
Because West Nile is a greater threat to immunologically vulnerable populations, developing a safer vaccine is a priority, the partners said.
Some of the initial vaccine-development costs will be defrayed by the NIAID grant, which the partners plan to use to evaluate candidate vaccine formulations in two unspecified animal models, scale up development and cGMP manufacturing of the lead candidate vaccine, and perform preclinical studies necessary for preparing an Investigational New Drug application and initiating Phase I clinical trials.
If all goes as planned, the partners hope to have a vaccine ready for such trials within three years, OHSU said.