Memorable Shot: Smallpox vaccine has lasting effect

The threat that the smallpox virus could be used by terrorists as a biological weapon has become a cornerstone of modern angst. Now, a research team finds reason to assuage some of that anxiety: People vaccinated against smallpox decades ago retain significant antibody and immune-cell responses against the dangerous virus.

“We’re finding long-term immunity,” says Mark Slifka of Oregon Health and Science University in Beaverton. At last week’s meeting of the American Society for Microbiology in Washington, D.C., Slifka and his colleague Erika Hammarlund reported the results of their survey of more than 300 people who had received one or more smallpox vaccinations over the past 75 years.

After a global immunization campaign against smallpox in the 1960s and 1970s, the disease was declared eradicated in 1980, and vaccinations were stopped. Fearful of an attack with the smallpox virus, however, the U.S. government recently began immunizing soldiers and health-care workers who would be the first to respond to an outbreak. Because the vaccine can have serious side effects, a debate has erupted over whether to widely vaccinate the public after an outbreak or just immunize people in the area where the outbreak occurs, a strategy called ring vaccination (SN: 4/5/03, p. 218: Available to subscribers at The Vaccinia Dilemma).

To inform that decision, researchers have developed computer models that predict how smallpox would spread given a range of factors. One of the biggest sources of uncertainty in such models has been whether people vaccinated decades ago remain immune. An online fact sheet from the Centers for Disease Control and Prevention in Atlanta, for example, declares, “Smallpox vaccination provides high level immunity for 3 to 5 years and decreasing immunity thereafter.”

Slifka, Hammarlund, and their colleagues took blood samples from one group of people who had received smallpox vaccinations between 20 and 75 years ago and another group of people who were immunized only recently. Then, in test tube studies, the scientists measured antibody and immune-cell responses to the virus.

The investigators found that more than 90 percent of the people vaccinated decades ago had an antibody response similar to the response of those recently vaccinated. The strength of the immune-cell response did decline with time, but virus-specific immune cells are still found in people vaccinated as long ago as the 1940s.

For Slifka, that finding all but settles the debate about how to respond to a new outbreak. “It would be unlikely that we would need to mass-vaccinate,” he concludes. “The ring-vaccination approach would be very effective.”

Not everyone agrees. Edward H. Kaplan of Yale University has modeled the spread of smallpox, including scenarios in which 50 percent of the public is already immune. “While [widespread immunity] would certainly reduce the number of deaths, it would still not tip me from recommending post-attack mass vaccination,” Kaplan says.

Making public policy on the basis of test-tube studies is a challenge, notes Jeff Frelinger of the University of North Carolina at Chapel Hill, who has documented continued immune responses to the smallpox virus in about a dozen people vaccinated decades ago. “While the long persistence of immune responses suggests resistance, there exist no studies to calibrate the [test-tube] responses measured with protection from smallpox following exposure.”

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