Researchers at the Medical College of Wisconsin have been studying vaccinia virus, which makes up the smallpox vaccine, for years as a way of understanding how viruses and vaccines work at the cellular level. That research, funded largely by the federal government, may lead to advances in preventing and treating smallpox, which could have ramifications in times of bioterrorism.
Vaccinia as Smallpox Vaccine
Vaccinia virus was one of the first vaccines ever developed. Smallpox had killed hundreds of millions of people through the centuries, but in the late 1700s medical practitioners noticed that milkmaids who had been exposed to cowpox were immune to smallpox. They began taking cowpox from cows and scratching it into the arms of people to protect them against smallpox. At some point, cowpox virus was replaced by vaccinia virus, which is 90% identical to smallpox but only rarely causes health problems.
Modern public health systems worldwide joined in a campaign to vaccinate populations against smallpox, and the dread disease was eradicated globally by the 1970s, at which point vaccination against the disease was discontinued. However, it is theoretically possible that a smallpox-like virus could re-emerge in nature as a result of the many poxviruses that exist in animal species. Furthermore, laboratories in the US and former Soviet Union are known to have stocks of the virus, perhaps refined as weapons. Other nations, potentially some that support terrorism, may also have stores of weaponized smallpox or the ability to produce it. Though unlikely, a smallpox attack would be highly contagious and could overwhelm communities if it occurs.
“As a first cousin of smallpox, vaccinia virus offers an ideal opportunity to study a complex and medically relevant virus,” says Paula Traktman, PhD, Walter Schroeder Professor and Chairman of the Department of Microbiology and Molecular Genetics at the Medical College of Wisconsin. She has headed a virus research laboratory since 1984 and moved to the Medical College in 1997. “Over the last 15-20 years there has been a revolution in the study of molecular genetics, which helps us understand how viruses work.” Vaccinia virus provides a model to understand universal biological processes that can affect everything from birth defects to cancer. As part of federal anti-bioterrorism initiatives, Dr. Traktman has also helped establish an international database to share all information pertinent to poxviruses and their vaccines.
Studying vaccinia virus helps researchers understand the “choreography of the viral lifecycle,” Dr. Traktman says. Researchers are examining how the virus enters cells and duplicates itself, synthesizing thousands of new viruses within the body that spread to other cells.
The researchers at the Medical College seek an alternative to the current smallpox vaccine by testing compounds for their ability to act at the intracellular level and serve as anti-viral drugs if an infection occurs. An anti-viral drug might act as protease inhibitors do in HIV-positive individuals, preventing the virus from multiplying. There is currently no antiviral drug to fight smallpox, although there is some laboratory evidence that cidovifir may have anti-viral properties after smallpox exposure. At this time, it has not been thoroughly tested and is not available for widespread use.
How Smallpox Spreads
It is estimated that during a smallpox outbreak in an urban setting, each infected person could infect 10 more people. Historically, smallpox kills about 30% of the people infected with it. If the vaccine is given within the first four days after exposure, it will prevent smallpox or significantly reduce the symptoms and risk of death. However, initial exposure is difficult to detect. Early on, there are only flu-like symptoms; there is no rash and it is not contagious. After about two weeks, pox (inflamed lesions) appear in the mouth and throat. Smallpox is highly contagious at that point and frequently spreads by coughing or even speaking. An extreme rash – hundreds of lesions – spreads to the face, arms and legs, leaving permanent scars.
Because smallpox virus can be spread through droplets and aerosols as a very fine mist, it could spread through ventilation systems within a building. Should an outbreak occur, infected individuals will be quarantined. The room – or building, if necessary – will be quarantined and pressurized so that air can flow in but not out. Bedding, clothing and even furniture may have to be destroyed because contagious dry pox may otherwise survive.
In case of a smallpox outbreak, vaccinations will likely be performed in a “ring” around the infected person. In other words, people who have had contact with the individual or contact with people who know the individual will receive vaccinations. Vaccinations of an entire region or the entire country are not expected to be necessary.
Because most physicians have never seen smallpox, the US Centers for Disease Control and Prevention has been providing educational materials and seminars to healthcare providers to help them recognize and treat smallpox outbreaks.
Will Childhood Vaccination Protect Against Smallpox?
There is some debate in the scientific community about whether people vaccinated against smallpox in childhood still have immunity from the disease. Dr. Traktman points to studies that show that while vaccination loses some of its efficacy over the years, immunity at the cellular level may last for decades. In other words, an individual vaccinated years earlier might become ill from smallpox, but is much less likely to die from it. They also may be less likely to transmit the disease. One study showed that even people over the age of 50 who were vaccinated as children retained significant immunity to smallpox. The biggest problem is that individuals born in the US since 1972 – tens of millions of people – have never been vaccinated for smallpox.
Smallpox vaccine is not currently available to civilians in the US, although the CDC has a small amount available for lab workers who use vaccinia virus and other poxviruses in their research. The US government currently has about 15 million of doses of smallpox vaccine available and has asked manufacturers to begin producing the vaccine in mass quantities in the event that smallpox is used as a bioterror weapon. By 2002 there should be enough vaccine for everyone in the country.
