New Agent Kills Influenza Virus, Prevents Infection In Mice

"These are preliminary, small-scale studies, but the results indicate this material called BCTP shows promise as a new weapon against the influenza A virus," says James R. Baker Jr., M.D., professor of internal medicine and director of the Center for Biologic Nanotechnology in the U-M Medical School. "Its main advantages are its rapid killing action, lack of specificity and the fact that it is non-toxic to skin and mucous membranes."

A milky-white emulsion of tiny lipid droplets suspended in solvent, BCTP was developed by D. Craig Wright, M.D., chief research scientist at Novavax, Inc., and president of Novavax Biologics Division. Novavax is a bio-pharmaceutical company located in Columbia, Md. According to Wright, the material is made of water, soybean oil, Triton X 100 detergent and the solvent tri-n-butyl phosphate.

In presentations at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) on Sept. 26, U-M research associates Andrzej Myc and Jon D. Reuter presented results of preliminary studies evaluating BCTP's effect on influenza A. Both research studies were funded by the Defense Advanced Research Projects Agency (DARPA) and directed by Baker.

Myc's study used Madin Darby Canine Kidney cells, used by researchers to evaluate the toxic effects of viruses. Myc incubated MDCK cells with influenza A virus and five different formulations of Novavax lipid structures. Using two different assay techniques, Myc then measured the number of cells infected with the virus. While all five formulations slowed the spread of the virus, BCTP was the most potent, reducing viral antigen levels by 99.6 percent.

In Reuter's study, different liquids were inserted into the nasal passages of four groups of laboratory mice. Control mice in Group 1 were given ordinary saltwater. Group 2 received BCTP alone. Group 3 received live influenza A virus and Group 4 was given a mixture of influenza A and BCTP. Groups 1, 2 and 4 stayed healthy, while all the mice in Group 3 developed severe pneumonia and two out of three mice died before the conclusion of the study.

"We learned several important things from these preliminary studies. The first is that BCTP is a highly effective killing agent for the influenza virus both at the cellular level and in living animals. Equally important is that BCTP had no toxic effects on nasal or lung membranes," Baker says. "We've shown that if we treat the virus with BCTP as it enters the nasal passages, we can prevent infection in mice. The next step is to see whether we can administer BCTP and the virus separately and still prevent infection. And the final step, of course, is to see whether it works as well in people as it does in mice."

While influenza vaccines are relatively effective at preventing the flu, Baker says there is a need for alternate preventive agents. "Influenza vaccines are expensive, they only are effective against a few viral strains each year and it takes time for immunity to develop. BCTP appears to inactivate the virus on contact."

The research is funded by DARPA's Unconventional Pathogen Countermeasures Program. The U-M and Novavax have filed a patent application covering BCTP's use as a decontamination agent for various anti-microbial applications. Baker is a member of the Novavax scientific advisory board, but has no significant financial interest in the company.