Journal
VIROLOGY
Volume 395, Issue 1, Pages 97-113Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.09.008
Keywords
Smallpox; Cowpox; Antigen discovery; Gene vaccine; DNA vaccine; Expression library immunization; Genomics
Categories
Funding
- Center for Innovations in Medicine
- National Institutes of Health [U54 AI057156]
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The licensed smallpox vaccine, comprised of infectious vaccinia, is no longer popular as it is associated with a variety of adverse events. Safer vaccines have been explored such as further attenuated viruses and component designs. However, these alternatives typically provide compromised breadth and strength of protection. We conducted a genome-level screening of cowpox, the ancestral poxvirus, in the broadly immune-presenting C57BL/6 mouse as an approach to discovering novel components with protective capacities. Cowpox coding sequences were synthetically built and directly assayed by genetic immunization for open-reading frames that protect against lethal Pulmonary infection. Membrane and non-membrane antigens were identified that partially protect C57BL/6 mice against cowpox and vaccinia challenges without adjuvant or regimen optimization, whereas the 4-pox vaccine did not. New vaccines might be developed from productive combinations of these new and existing antigens to confer potent, broadly efficacious protection and be contraindicated for none. (C) 2009 Elsevier Inc. All rights reserved.
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