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CCSV (Cell-Cultured Smallpox Vaccine) is a second-generation, live-attenuated vaccinia virus vaccine developed by DynPort Vaccine Company (DVC) under contract with the U.S. Department of Defense. It was designed as a modern replacement for Dryvax, the traditional calf-lymph-derived vaccine. CCSV is produced using MRC-5 human diploid cell cultures, which offers a more controlled and sterile manufacturing process compared to animal-derived methods. The vaccine utilizes a cloned version of the New York City Board of Health (NYCBOH) vaccinia strain. Clinical development reached Phase 2, where it was evaluated for safety, reactogenicity, and its ability to produce a "take" (a characteristic skin lesion indicating successful vaccination). Although it demonstrated comparable immunogenicity to Dryvax, it was not the primary vaccine selected for the U.S. Strategic National Stockpile, a role filled by ACAM2000.
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