vaccination began, 6.7 million doses of the undiluted Dryvax vaccine were approved for distribution as a licensed vaccine: 1 million doses for use in the military vaccination program, and the remaining 5.7 million doses for the Department of Health and Human Services to be used for smallpox preparedness vaccination activities. New vaccine then under production was not expected to be available as a licensed product until 2004, but in the event of a smallpox release, the government planned to use available vaccine under Investigational New Drug protocol for mass vaccination.

In September 2000, CDC awarded Acambis Inc. a contract for a stockpile of 40 million doses of smallpox vaccine, and the contract was later increased to 54 million doses (DHHS, 2001). In November 2001, a second contract was awarded by DHHS to Acambis in partnership with Baxter Healthcare Corporation to produce an additional 155 million doses of vaccine for the U.S. government (DHHS, 2001). Although the Acambis vaccines, ACAM1000 and ACAM2000, are also derived from the NYCBH strain, they are grown in two types of cell culture rather than on the skin of a calf (Dryvax) (FDA, 2004). The Department of Defense is also supporting the clinical development of a cell culture vaccine by DynPort Corporation (PRNewswire, 2002).

Vaccine Safety

Vaccination is an effective public health tool in cases where the known risks of the vaccine are weighed against the known benefits of the vaccine and the risk of disease. Smallpox vaccination is known to cause generally mild symptoms and only rarely has resulted in more severe infection or death. Given the remarkable severity of smallpox disease, and the high effectiveness of the vaccine, the risk-benefit ratio was very clear while the disease was endemic. Historic objections to vaccination were made on moral or philosophical grounds and not on the basis of vaccine safety. It had always been known that smallpox vaccine was not innocuous, and as smallpox cases dropped to zero in industrialized nations, the adverse outcomes related to vaccination became more worrying. The case-fatality rate for smallpox vaccines in 1968 was one per one million primary vaccinations, and children had higher rates (number of events per million primary vaccinees) of severe vaccine-related complications when compared with primary vaccinees age 20 and older (Breman and Henderson, 2002). This was part of the reason the United States halted vaccination of the general public in 1972. At the end of the century, analysis of the risks posed by the vaccine could only be assessed in the context of a disease presenting no cases, leading to a significantly different risk-benefit balance.

Vaccine safety findings must also be viewed in the context of differ-

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