West Coast Editor

Continuing their efforts to head off bioterrorism, the feds awarded hefty grants that will benefit a pair of West Coast firms in their separate bids for a vaccine against Francisella tularensis, the fast-moving bug that causes tularemia - the inhaling of which leads to a deadly form of pneumonia.

"It's on the Category A list for biothreats," said Rick Lyons, associate professor of medicine at the University of New Mexico, who is leading a consortium with efforts focused on using Concord, Calif.-based Cerus Corp.'s KBMA vaccine technology.

"There is a vaccine out there, but it's been difficult to move it along because of a lack of understanding about its mechanism of protection and its attenuation."

That vaccine "is safe and it works, but it's not up to modern-day standards," Lyons told BioWorld Today. "We expect a lot more of our vaccines now. We want to know why they are protecting and why they are safe."

Under the terms of the contract from the National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health), Cerus gets $2.8 million from the $23 million total over a period of three years. Other members of the consortium are Lovelace Respiratory Research Institute, in Albuquerque, N.M., Arizona State University, and the University of Texas at San Antonio.

Cerus' KBMA approach involves dead but metabolically active bacteria. The KBMA technology bases the vaccine on the whole microorganism, thus getting around the challenge of figuring out the relevant antigens to target.

Using germs with engineered deletions in a widely shared DNA-repair pathway, the KBMA vaccines are killed by introducing crosslinks in their genomes, which blocks replication of their DNA. Since most genes can be transcribed to mRNA, protein synthesis is mostly unaffected, so the KBMA bacteria behave metabolically and immunologically as if they are active - while not causing infection.

A paper on the method, "Killed But Metabolically Active (KBMA) Microbes: A New Vaccine Paradigm For Eliciting Effector T-Cell Responses And Protective Immunity," was published in the August 2005 issue of Nature Medicine.

Lyons called Cerus' KBMA method "very interesting," but said, "I think they would admit there are challenges to their technology that we hope to help them figure out."

Sometimes called rabbit fever because that animal is the one that most often carries the germ, tularemia - which is typically treated with antibiotics - also is passed under normal conditions by bites from deer flies and ticks.

But it's not normal conditions that the government is worried about. Although humans have not been known to infect each other, only a small number of bacteria - about 10 to 50 organisms - can cause the disease by other means. The Centers for Disease Control and Prevention said that, if Francisella tularensis were used as a bioweapon, the bacteria likely would be made airborne so they could be inhaled. The incubation period typically is three to five days.

"Our primary goal is to develop appropriate models that will allow us to test these vaccines that people are working on," Lyons said. "Lovelace and ourselves are developing the models to advance the vaccines. Cerus and Arizona State are working on vaccine candidate discovery."

Lyons foresees "a whole new paradigm of vaccine generation. It's going to take something different than the way we've done it before, because [many new infections] crop up that are very localized - either population restricted or geographically restricted."

As an example, he cited the Hanta virus, spread through contact with rodent waste, which made headlines a few years ago, especially in the Southwest.

"It's a devastating disease, but it doesn't impact very many people," Lyons said.

Among other biotechnology firms recently to become involved in the tularemia push is Dynport Vaccine Co. LLC (DVC), of Frederick, Md., which is part of Computer Sciences Corp., of El Segundo, Calif. Also involved is EpiVax Inc., of Providence, R.I.

The genome sequence of F. tularensis was reported in January by scientists at the United Kingdom's Defence Science and Technology Laboratory at Porton Down, according to BioWorld's Biodefense Market Report 2005. The genome, which is 1.9 million base pairs, was mapped over five years by researchers from the UK, the U.S. and Sweden.

Disclosed (as was the Cerus news) Wednesday was the five-year, $35.1 million NIAID contract to Computer Sciences Corp. (CSC). Under the terms, DVC will develop and optimize preclinical testing models, assess immune response and develop new tularemia vaccine candidates, with help from Umea University in Sweden, the Defence Science and Technology Laboratory, which is a component of the United Kingdom's Ministry of Defense, and the National Research Council of Canada.

DVC is a biodefense firm that belongs to CSC's Enforcement, Security and Intelligence organization, which the parent company created in 2001 to support programs enhancing U.S. security. CSC's focus otherwise is information technology.