New classes of orthopoxvirus vaccine candidates by functionally screening a synthetic library for protective antigens.
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.
Borovkov
Alexandre
A
Center for Innovations in Medicine at The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Magee
D Mitch
DM
Loskutov
Andrey
A
Cano
Jose A
JA
Selinsky
Cheryl
C
Zsemlye
Jason
J
Lyons
C Rick
CR
Sykes
Kathryn
K
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D015608:Cowpox virus / Q000235:genetics* / Q000276:immunology; D005260:Female; D015723:Gene Library; D016679:Genome, Viral; D051379:Mice; D008810:Mice, Inbred C57BL; D016366:Open Reading Frames; D013601:T-Lymphocytes / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D014765:Viral Vaccines