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

作者：Borovkov Alexandre; Magee D Mitch; Loskutov Andrey; Cano Jose A; Selinsky Cheryl; Zsemlye Jason; Lyons C Rick; Sykes Kathryn^*

来源：Virology, 2009, 395(1): 97-113.

DOI：10.1016/j.virol.2009.09.008

• Smallpox
• Cowpox
• Antigen discovery
• Gene vaccine
• DNA vaccine
• Expression library immunization
• Genomics

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.

• 出版日期2009-12-5