To counter the virus's mutability, Carver suggests developing a wider array of antivirals. The National Institutes of Health
(NIH) seems to agree: Earlier this spring, NIH approached representatives at BioCryst Pharmaceuticals to ask the Alabama company
to restart research and development on peramivir, a neuraminidase inhibitor the company began developing in the late-90s but
shelved in 2002 due to poor clinical results. Unlike scientists at Gilead, BioCryst was unable to package peramivir in an
easily soluble pill, but this time around the company will try to formulate the compound as an injectable. Phase I testing
in humans is expected to begin next month.
In addition, because of the sudden surge of investors in antivirals, Carver says scientists from six different academic labs
around the world have approached ICAV for help in revitalizing their previously stagnant antiviral research. "I believe it's
been shortsighted on the part of governments to think they can rely on just one," Carver says. "The evidence is there that
resistance is likely to emerge rapidly to Tamiflu, and therefore second and third-line treatments make sense."
The long-term solution, however, is still vaccines. Building an effective pandemic vaccine may be difficult—and designing
a perfect one is likely impossible—but companies are still trying.
Kathleen Coelingh, MedImmune scientist
Sanofi-Pasteur, the vaccine branch of the French conglomerate Sanofi-Aventis, won a $100 million contract from the US Department
of Health and Human Services in September 2004 to produce two million doses of an H5N1 vaccine in bulk concentrate form. In
March Sanofi delivered 8,000 doses of an experimental H5N1 vaccine to the National Institute of Allergy and Infectious Diseases
(NIAID), part of NIH, where researchers tested the vaccine in healthy adults to determine the ideal dosage. The vaccine was
then sent to Vanderbilt University in October, where researchers ran efficacy and safety tests on elderly patients and children.
Tom Talbot, MD, a Vanderbilt assistant professor of medicine involved in the research, says the goal of the tests were to
see "if a vaccine could be produced easily using our existing infrastructure."
Since the vaccine is being developed using a specific strain of H5N1—extracted from a person who was infected in southeast
Asia last year—the vaccine isn't expected to offer complete protection. But Talbot notes, "You want to make sure that the
process you're developing is safe." And in case of an outbreak, the vaccine offers hope for at least partial protection.
Meanwhile, other companies are working on less conventional products. MedImmune, the only vaccine manufacturer based in the
US, signed a cooperative research and development agreement with NIAID on September 27 to design a pandemic vaccine using
a live, attenuated virus. The development builds upon 40 years of research. MedImmune has a seasonal flu vaccine called FluMist,
launched in 2003, that uses a live, attenuated virus, but the product hasn't been very popular. "Sometimes it takes a few
years before people get accustomed to the idea that there is a new and potentially better way of protecting yourself," says
Kathleen Coelingh, MedImmune's senior director of scientific affairs, who expects this year's sales of FluMist to increase.
The process of attenuating a live virus begins by cold-adapting it in cell culture. The virus is grown in progressively lower
temperatures until it loses its ability to attack cells at body temperature, rendering it safe to introduce into humans. But
the virus retains its shape and ability to replicate, so it becomes a sitting duck for the body's immune system.
The novelty of MedImmune's product lies in a "master strain" called the Master Donor Virus (MDV), which acts as a vehicle
for attenuating other strains of influenza. Over a 30-year period, NIAID scientists attached about 20 different strains of
influenza to the MDV and showed that they were all harmless when introduced into people.