New classes of orthopoxvirus vaccine candidates by functionally screening a synthetic library for protective antigens.

Abstract

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.

• Authors: Alexandre Borovkov, D Mitch Magee, Andrey Loskutov, Jose A Cano, Cheryl Selinsky, Jason Zsemlye, C Rick Lyons, Kathryn Sykes
• Journal: Virology (Virology) Vol. 395 Issue 1 Pg. 97-113 (Dec 05 2009) ISSN: 1096-0341 [Electronic] United States
• PMID: 19800089 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Viral
• Antigens, Viral
• Viral Vaccines

Topics

• Animals
• Antibodies, Viral (blood, immunology)
• Antigens, Viral (genetics, immunology)
• Cowpox virus (genetics, immunology)
• Female
• Gene Library
• Genome, Viral
• Mice
• Mice, Inbred C57BL
• Open Reading Frames
• T-Lymphocytes (immunology)
• Viral Vaccines (genetics, immunology)