Contributing Writer

WASHINGTON - On the same day Acambis plc announced that it had suspended trials for its lead smallpox vaccine, Thomas Monath, the company's chief scientific officer at its facility in Cambridge, Mass., described breakthroughs in new vaccine development.

Monath, speaking Tuesday at the State of the Art in Biodefense Vaccines and Therapeutics symposium in Washington, described the smallpox vaccine as an improvement to the old Dryvax smallpox vaccine. He said the company is still pursuing the fulfillment of a stockpile of 209 million doses for the U.S. government.

But that smallpox vaccine does not represent Acambis' contribution to new vaccine technology. Monath talked about recent work in creating chimeric live attenuated vaccines, using yellow fever 17D combined with envelope genes for other flaviviruses. Those include new vaccines in development for Japanese encephalitis, Dengue and West Nile virus, among others. The Acambis ChimeriVax system is in a third Phase II trial for Japanese encephalitis, a Phase I trial for Dengue has been completed and a Phase I trial for West Nile virus infection is in progress.

Another company, AlphaVax, is developing its Alphavirus Replicon Vector ArV vaccines derived from an avirulent form of Venezuelan equine encephalitis virus, with genes related to the vaccine target substituted. The Research Triangle Park, N.C., company has used that system to develop vaccines for many biological threat agents, including the marburg, lassa and ebola viruses.

Perhaps the best-known biological threat is anthrax, or bacillus anthracis. However, naturally occurring cases infecting man are extremely rare - it took the spore-containing letters in the U.S. in 2001 to show how vulnerable humans are to the bacterium and other biological threats. But estimates show that a single airplane spraying an aerosol with anthrax spores could infect or kill anywhere from 130,000 to as many as 3 million people, depending on meteorological conditions, said Arthur Friedlander, senior scientist/senior adviser at U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).

Louis Pasteur discovered the first live, attenuated vaccine for anthrax in 1881, but advances in vaccine development didn't lead to licensure of a human vaccine in the U.S. until 1970 (AVA/Biothrax vaccine, from Bioport Corp.) and in the UK in 1979. That is the vaccine currently in use.

Many new approaches are being developed for anthrax vaccines, including protein vaccines, live attenuated vaccines and a variety of other technologies. One approach, studied at USAMRIID for the past 10 years, has been recombinant protective antigen (rPA) vaccines. A non-spore forming avirulant B. anthracis strain was used to make those vaccines and has been shown effective in protecting both rabbits and non-human primates. Friedlander said there are several candidate rPA vaccines now in Phase I trials.

On the smallpox front, Bernard Moss, chief of the laboratory of viral diseases of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., cited numerous pursuits of new vaccines, including many attenuated strains, most notably, a modified vaccinia virus ankara (MVA) vaccine, and the combination use of multiple recombinant protein vaccines.

In addition to the development of new vaccines, new routes of administration are being developed. Acambis, in a joint venture with Becton, Dickinson & Co., of Franklin Lakes, N.J., is developing an OnVax wipe-and-go system for gently scraping down the outer layer of skin to allow administration of Acambis' ChimeriVax vaccines directly to the dendritic cells.

Protection against biological threat agents also can include new therapeutics to treat the disease and in some cases provide a protection against exposure. One advance, from the University of California at San Francisco, is the development of monoclonal antibodies for use with botulinum neurotoxin. The university's James Marks said monoclonals also are being investigated with other biological threat agents including smallpox, Y. pestis (plague), and hemorrhagic fever viruses such as ebola.

The conference ends today.