How did ACAM2000 differ from earlier smallpox vaccines?

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Smallpox vaccination — smallpox Edward Jenner vaccinating his child against smallpox; colored engraving.

Approved by the U.S. Food and Drug Administration in 2007, ACAM2000 was the first new smallpox vaccine licensed in the United States since 1931.12

Unlike earlier vaccines that were historically harvested from the skin of inoculated calves, ACAM2000 is produced using modern cell culture techniques—specifically utilizing African Green Monkey kidney (Vero) cells. This manufacturing process allows for the rapid production of the vaccine in large quantities, which is essential for emergency preparedness in the event of a smallpox outbreak.132

While ACAM2000 remains a live, replication-competent vaccinia-based vaccine, it represents a significant advancement in production technology compared to the traditional methods used during the 19th and 20th centuries.12