KEEPING ONE STEP AHEAD OF SMALLPOX
By Ruth Marvin Webster
North County Times
November 6, 2004 - If you are an American older than 30, chances are you were vaccinated for smallpox before you started kindergarten. You may remember how many of your friends sported small scars on their upper arms, or how your red, itchy bump turned into a scab and then fell off a couple of weeks later.
Nowadays, those badges of childhood are noticeably absent on school ball fields. Gone also is the immunity millions used to enjoy against the viriola virus, the virus medical historians believe has killed more people than any other infectious disease. That fact has some terrorism experts concerned about how we might fare if the smallpox virus was developed as a biological weapon.
This heightened awareness of biological weapons has prompted the federal government to increase research dollars for biodefense by some 30 percent, said Mitchell Kronenberg, president and head scientific director of the La Jolla Institute for Allergy and Immunology.
In fact, the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health, recently awarded 14 contracts totaling more than $73 million to fund an initiative aimed at generating research data relating to the body's immune system to infectious disease agents such as smallpox.
Two of those contracts went to the La Jolla Institute for Allergy and Immunology to develop an immune epitope database, which will help map the immune system. The grants are part of the NIH's new Large Scale Antibody and T Cell Epitope Discovery program.
Recognized by the body's white blood cells, epitopes are small sites on a large molecule that are the focus of an immune response.
"We're pleased that the NIH has entrusted the Institute not only with creating and hosting this important database, but also with the work of gathering much of the data related to the smallpox and arena viruses," Kronenberg said.
Dr. Alessandro Sette, the institute's head scientist on the five-year project, said his team's research is part of a national drive to develop a safer smallpox vaccine.
"Because the vaccine was developed so long ago," he said, "before the advent of modern technologies, little is known about exactly how the vaccine works to generate the appropriate immune response."
"It is time for an improved vaccine," he continued. "With the use of new technology such as large computer modeling and bioinformatics, we can do things now that we could have only dreamed of 10 years ago."
Sette and his team expect the database will allow researchers around the world to access crucial information about the way the body responds to disease-causing agents. It is the first time that scientists will create a map of the immune response to the smallpox vaccine. The map will detail thousands of biochemical and cellular activities, and help scientists develop a newer and safer smallpox vaccine or perhaps a first-time-ever vaccine to safeguard against viruses.
And since the database will include data about other viruses, such as those that cause meningitis and hemorrhagic fever, the scientists are hopeful the project will translate into increased understanding of lesser-known, emerging diseases.
"There is a tendency to feel we have conquered infectious disease because of our success against polio, tuberculosis and the eradication of smallpox," Kronenberg said. "But there are always new flu viruses, SARS ---- even HIV, which is really only 20 years old ---- so we must always stay vigilant."
"It is war," said Sette, who heads the institute's Vaccine Discovery division. "Nature keeps coming up with new dangerous viruses, and researchers study them to try to figure out how to combat them. There is a constant tension with us trying to keep one step ahead of the germs."
Founded in 1988, the La Jolla Institute for Allergy and Immunology is a nonprofit medical research center devoted to better understanding the human immune system. With a staff of more than 100 researchers, the institute is planning to move to a new building on the UC San Diego campus in 2006.
In the meantime, the institute's facilities are in the heart of San Diego's biotech community, in Torrey Pines Mesa, just a step away from UC San Diego, the Scripps Research Institute, the Torrey Pines Institute for Molecular Studies and, of course, the Salk Institute, which was founded by none other than Jonas Salk, who gave the world the polio vaccine. It is a fact not lost on Kronenberg.
"This area is a very special place for immunology and vaccine research," he said. "I think we are taking a leading role in that tradition."
Since the worldwide eradication of smallpox in 1980, say the Working Group on Civilian Defense of the American Medical Association ("Management of Smallpox Used as a Biological Weapon" JAMA, June 9, 1999), the storage of the virus was restricted to two laboratories ---- one in the US and the other in Russia ---- but with the collapse of the Soviet Union, it has been reported that secret stockpiles of the virus have been held by a handful of rogue nations. There was even some evidence that Iraq stockpiled smallpox.
While the government has stopped short of recommending the general public be vaccinated against smallpox, military servicemen and women continue to be inoculated before they are deployed and here, at home, health-care workers and emergency workers such as firefighters and the police are also being vaccinated.