In addition to the currently licensed smallpox vaccine, Dryvax, there are several other smallpox vaccines that are currently being evaluated in clinical investigations under Investigational New Drug Applications (IND). In September 2000, Acambis Inc. was awarded a contract by the Centers for Disease Control and Prevention to create a stockpile of 40 million doses of smallpox vaccine, and the contract was later increased to 54 million doses. In November 2001, a second contract was awarded by the Department of Health and Human Services (DHHS) to Acambis in partnership with Baxter Healthcare Corp. to produce an additional 155 million doses of vaccine for the U.S. government. The vaccines being produced by Acambis for these contracts, ACAM1000 and ACAM2000 respectively, are derived from the same vaccine strain as Dryvax, but are grown in cell culture (as opposed to the skin of a calf used for Dryvax). ACAM1000 is grown in cells of human origin called MRC-5 cells, and ACAM2000 is grown in cells of monkey origin called Vero cells. Depending on the safety and efficacy profiles of these vaccine candidates seen in the clinical trials under IND, as well as other considerations, the manufacturer may seek approval for their products. A description of the vaccine product approval process can be found on our Vaccine Product Approval Process page. The National Institute of Allergy and Infectious Diseases (NIAID) is supporting studies of other smallpox vaccines under IND. A summary of the current studies in progress can be found on the NIAID web site. Additional information about the design of these trials is also available (enter "smallpox" into the query field). Currently, NIAID is conducting studies in adults to evaluate the safety and efficacy of various concentrations of a smallpox vaccine that was manufactured by Aventis Pasteur Inc. Like Wyeth's Dryvax, the Aventis Pasteur vaccine was derived from the NYCBH strain of vaccinia and grown on the skin of calves. The existing supplies of this vaccine were manufactured prior to the cessation of routine smallpox immunization in the United States. This vaccine was an approved vaccine until 1997, when, due to the long-standing discontinuation of routine smallpox vaccination, Aventis Pasteur requested revocation of their license. Stocks of the vaccine have remained frozen since manufacture and could be made available for emergency use under the IND process. In 2002, NIAID evaluated the Aventis Pasteur vaccine in a pilot study, and found that it elicited a high "take" rate in previously unvaccinated individuals. Additional IND studies are ongoing. In addition, the DynPort Vaccine Company is sponsoring the clinical development of a new cell-cultured vaccine (CCSV) that is also derived from the NYCBH strain of vaccinia. This activity is being performed under a Department of Defense contract. NIH is supporting the study of new generation smallpox vaccines that are made using even more attenuated, or weakened, forms of the smallpox vaccine virus. One such attenuated vaccine is referred to as modified vaccinia Ankara (MVA), a potential alternative smallpox vaccine that is under study based on the hope that it might be both safe and effective for individuals at high risk of complications from existing smallpox vaccines. A summary of the NIAID sponsored phase 1 trial of this vaccine candidate is available. | 
