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

Virology. 2009 Dec 5;395(1):97-113. doi: 10.1016/j.virol.2009.09.008. Epub 2009 Oct 2.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Viral Vaccines