NIH Awards Pitt Medical School $1.3 M to Develop Promising Avian Flu Vaccine

The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health in Bethesda, Md., has awarded a $1.3 million, two-year grant to Pitt’s School of Medicine to produce a promising avian flu vaccine that could be used in Phase I and Phase II human clinical trials.

In January of this year, Pitt researchers reported in the journal Virology that their vaccine, which contains critical components of the deadly H5N1 virus but does not cause disease, completely protected mice and chickens from infection after exposure to the wild-type virus.

According to Andrea Gambotto, assistant professor in the Pitt medical school’s Department of Surgery and Department of Molecular Genetics and Biochemistry and lead investigator on the project, the funding will allow his group to begin immediate scale-up of vaccine production.

“It will take us a few weeks to get our facility ready.  However, we hope to begin vaccine production by early fall,” he said.

Gambotto and his coworkers created their vaccine by genetically engineering a common cold virus, called adenovirus, to express either all or parts of an avian influenza protein called hemagglutinin (HA) on its surface. Found on the surface of all influenza viruses, HA allows the virus to attach to and infect a cell, a critical step in the influenza virus’ ability to cause illness and death.

Because this vaccine contains a live virus, Pitt investigators believe it may be more effective in stimulating a therapeutic immune response than avian flu vaccines prepared by traditional methods. Indeed, traditionally developed flu vaccines—in which the virus is grown in fertilized chicken eggs and then killed by heat or chemicals—take a minimum of four to six months to make and typically produce an immune response against only one strain of the virus. Since there is evidence that H5N1 is beginning to mutate, more traditional vaccines might have limited effectiveness in a pandemic outbreak.

Because the Pitt vaccine is grown in cells, it can be produced much more quickly, making it an extremely attractive candidate for preventing the spread of the virus in both domestic livestock populations and in humans. There also is evidence from other studies that such vaccines can protect against more than one strain of the virus. Since their initial report, Gambotto’s team has refined the vaccine by adding more H5N1 immune-stimulating proteins, which they believe will make it even more effective against different strains of the virus.

Gambotto hopes that NIAID will be interested in comparing the effectiveness of his vaccine to that of two other vaccines that already have been tested in federally funded clinical trials. Those vaccines, produced by GlaxoSmithKline and Sanofi Pasteur, stimulated what is considered an adequate immune response in only one-half to three-quarters of healthy people who were inoculated.

“Testing our vaccine in the same protocol as the previous two is the only way to tell if ours
is as good, better, or worse,” Gambotto explained.

To date, H5N1 has caused the most large-scale and widespread bird deaths in known history—an estimated 150 to 200 million birds have died in the outbreaks or been killed as part of infection-control actions in the last eight years. The H5N1 virus does not usually infect humans. However, in 1997 the first case of spread from a bird to a human occurred in Hong Kong during an outbreak of bird flu in poultry. The virus caused severe respiratory illness in 18 people, six of whom died. Since that time, there have been 241 known human cases of
infection with H5N1, and 141 of those have died, according to the World Health Organization.