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

• Published in: Virology (New York, N.Y.) Vol. 395; no. 1; pp. 97 - 113
• Main Authors: Borovkov, Alexandre, Magee, D. Mitch, Loskutov, Andrey, Cano, Jose A, Selinsky, Cheryl, Zsemlye, Jason, Lyons, C. Rick, Sykes, Kathryn
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.12.2009
• Subjects: Animals; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigen discovery; Antigens, Viral - genetics; Antigens, Viral - immunology; Cowpox; Cowpox virus - genetics; Cowpox virus - immunology; DNA vaccine; Expression library immunization; Female; Gene Library; Gene vaccine; Genome, Viral; Genomics; Infectious Disease; Mice; Mice, Inbred C57BL; Open Reading Frames; Orthopoxvirus; Poxvirus; Smallpox; T-Lymphocytes - immunology; Viral Vaccines - genetics; Viral Vaccines - immunology; Gene vaccine; DNA vaccine; Smallpox; Expression library immunization; Cowpox; Genomics; Antigen discovery
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2009.09.008

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.