Nature Medicine9, 1125 - 1130 (2003)
Published online: 17 August 2003; | doi:10.1038/nm916
Clonal vaccinia virus grown in cell culture as a new smallpox vaccine
Richard Weltzin1, Jian Liu1, Konstantin V Pugachev1, Gwendolyn A Myers1, Brie Coughlin1, Paul S Blum1, Richard Nichols1, Casey Johnson2, John Cruz3, Jeffrey S Kennedy3, Francis A Ennis3
& Thomas P Monath1
1
Acambis Inc., 38 Sidney Street, Cambridge, Massachusetts 02139, USA.
2
PRA International, 16300 College Boulevard, Lenexa, Kansas 66219, USA.
3
Center for Infectious Disease & Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
Although the smallpox virus was eradicated over 20 years ago, its potential release through bioterrorism has generated renewed interest in vaccination. To develop a modern smallpox vaccine, we have adapted vaccinia virus that was derived from the existing Dryvax vaccine for growth in a human diploid cell line. We characterized six cloned and one uncloned vaccine candidates. One clone, designated ACAM1000, was chosen for development based on its comparability to Dryvax when tested in mice, rabbits and monkeys for virulence and immunogenicity. By most measures, ACAM1000 was less virulent than Dryvax. We compared ACAM1000 and Dryvax in a randomized, double-blind human clinical study. The vaccines were equivalent in their ability to produce major cutaneous reactions ('takes') and to induce neutralizing antibody and cell-mediated immunity against vaccinia virus.
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