Gigi Kwik of the Center for Civilian Biodefense Strategies at Johns Hopkins University explains.

Edward Jenner, the English physician who first developed the smallpox vaccine in 1796, believed that vaccination caused a fundamental change in personal constitution and would lead to lifelong immunity to smallpox. Unfortunately, this proved to be incorrect. It is now clear that immunity wanes over time. Exactly how long the vaccine confers protection, however, is difficult to assess.

Immunity to smallpox is believed to rest on the development of neutralizing antibodies, levels of which decline five to 10 years after vaccination. This has never been satisfactorily determined, though. And because smallpox has been eradicated in the wild, correlating antibody levels with susceptibility is not possible. Revisiting historical data is difficult because of incomplete information in a number of areas. These include how many times the subjects were vaccinated (revaccination produces longer-lasting immunity), whether the vaccinations were carried out successfully and whether or not subjects ever had a subclinical smallpox infection that would boost their immunity (this situation is particularly likely in endemic areas). The last natural smallpox infection occurred in 1977, so recent advances in immunology and medical testing cannot be brought to bear on this question.

Before smallpox was eradicated, the World Health Organization (WHO) recommended that international travelers to nonendemic countries should be revaccinated every five to 10 years and travelers to endemic countries should be revaccinated every three years. Lab workers in diagnostic facilities and others more likely to be exposed to the smallpox virus were advised to be vaccinated once a year. The basis for the WHO guidelines was that a history of vaccination within five years was known to offer good protection, whereas the data for vaccination beyond 10 years was difficult to interpret. A conservative estimate of the duration of smallpox immunity was therefore justified.

Vaccination 40 years ago, even if not currently protective against smallpox disease, may offer some protection against a fatal outcome. A study of smallpox cases imported into nonendemic countries found that mortality was 52 percent among the unvaccinated, 11 percent among those vaccinated more than 20 years earlier and 1.4 percent of those vaccinated within 10 years. Therefore, vaccination 40 years ago most likely does not confer protection against smallpox infection, but it may help to prevent a fatal outcome. Should you be exposed to smallpox in the future, you should definitely be revaccinated because vaccination after exposure to an infected smallpox patient, even four days later, can prevent smallpox disease.

People that are revaccinated are, in general, much less likely to suffer from vaccine side effects than those vaccinated for the first time, although changing life circumstances (such as pregnancy, an impaired immune system or the need to take immunosuppressive drugs) can increase the risks. Most of the data about revaccination comes from a Centers for Disease Control and Prevention study in 1968, which found that of the 8.5 million people revaccinated that year, no one developed postvaccinial encephalitis, an often fatal complication that can occur in otherwise healthy people vaccinated for the first time. Six individuals (of which two died) developed progressive vaccinia, a condition that only occurs when there is an immune deficiency. Eight people developed and recovered from eczema vaccinatum, a condition in which vaccinia pustules develop on sites of the body (not necessarily the vaccination site) that either were affected, or had a history of being affected, by eczema. Ten people developed and recovered from generalized vaccinia, a rash known to occur a week or so after vaccination in otherwise healthy people. People who suffer from progressive vaccinia, generalized vaccinia or eczema vaccinatum are treated with vaccine immunoglobulin, a preparation of antibodies to the vaccinia virus obtained from the plasma of recently vaccinated donors.

There are two types of smallpox vaccine that would be administered in the event of an outbreak in the U.S. Both vaccines use the same strain of vaccinia virus, the so-called New York Board of Health strain, and they differ only in the way they are prepared. The old Dryvax vaccine, made in the 1970s by Wyeth Laboratories, was made by purifying vaccinia virus obtained from pustules removed from deliberately infected cows. The vaccine currently produced by Acambis-Baxter Laboratories is made using modern tissue-culture methods: the vaccinia is grown in cells in a laboratory and then purified.