ABSTRACT
On May 14, 1796, Edward Jenner inoculated 8-year-old James Phipps with cowpox virus obtained from an infection on the hand of Sarah Nelmes, a milkmaid. Subsequent events established that this simple procedure provided complete protection against smallpox and formed the basis for its ultimate eradication: The last case of endemic smallpox was in 1977 [1]. The prophylactic effect of vaccination was due to the close genetic and antigenic relationships between variola virus, the causative agent of smallpox, and its more benign relatives cowpox virus and vaccinia virus. The latter virus may have been isolated from an infected horse and, presumably because of its milder reactivity, was substituted for cowpox virus [2]. Vaccinia virus was economical to produce, active in low amounts, heat stable, resistant to freeze drying, simple to administer, relatively safe, and provided long-lasting immunity. Of equal importance for smallpox eradication, however, were the ease of diagnosis of the disease, variola’s lack of antigenic variation, and the absence of latently infected human or animal reservoirs. Although the vaccine was immediately successful, eradication of smallpox proved difficult for logistical reasons. In 1967, the World Health Organization implemented a new intensified global ring vaccination strategy that ultimately contained and eliminated variola virus from nature. Nevertheless, registered stocks of variola virus are preserved in both the United States and Russia. With the eradication of smallpox, the general need for vaccination was eliminated and the practice largely stopped. As a result, most people are now susceptible to variola virus, as well as other orthopoxviruses such as monkeypox virus. As a precaution against the possible reintroduction by terrorists of variola virus from an unregistered stock, a new tissue-culturederived vaccinia virus vaccine will soon be available. In addition, attenuated strains of vaccinia virus are being evaluated as safer alternatives to the conventional vaccine.
