Vaccine Attenuation via Deoptimization of Synonymous Codons


Research scientists at CDC have developed compositions and methods that can be used to develop attenuated vaccines having well-defined levels of replicative fitness and enhanced genetic stabilities. Infections by intracellular pathogens, such as viruses, bacteria, and parasites, are cleared in most cases after activation of specific T-cell immune responses that recognize foreign antigens and eliminate infected cells. Vaccines against those infectious organisms traditionally have been developed by administration of whole live attenuated or inactivated microorganisms. Although research has been performed using subunit vaccines, the levels of cellular immunity induced are usually low and not capable of eliciting complete protection against diseases caused by intracellular microbes. CDC inventors discovered that replacement of one or more natural (or native) codons in a pathogen with synonymous unpreferred codons can decrease the replicative fitness of the pathogen, thereby attenuating the pathogen. The unpreferred synonymous codon(s) encode the same amino acid as the native codon(s), but have nonetheless been found to reduce a pathogen's replicative fitness.

Potential Commercial Applications: Competitive Advantages:
  • Vaccine design and development
  • Functional improvements for current vaccines
  • Increasing the phenotypic stability of live attenuated vaccines
  • Attenuation optimization endeavors
 
  • Retains the protective and immunogenic advantages of native-codon live attenuated vaccine strains
  • Alleviates some critical safety issues associated with using live attenuated vaccines
  • Likely to possess greater long-term genetic stability than single-point mutations (fewer reversions)


Development Stage:
In vitro data available

Inventors:

Olen Kew (CDC)  ➽ more inventions...

Cara Burns (CDC)  ➽ more inventions...

Jacueline Quay (CDC)  ➽ more inventions...

Jing Shaw (CDC)  ➽ more inventions...


Intellectual Property:
US Pat: 8,846,051 issued 2014-09-30
PCT Pat: 10,695,414 issued 2020-06-30
US Application No. 11/576,941 filed on 2007-11-19
US Application No. 14/464,619 filed on 2014-08-20
US Application No. 15/684,355 filed on 2017-08-23
US Application No. 15/994,074 filed on 2018-05-31
US Application No. 15/931,336 filed on 2020-05-13
Various international patent applications pending or issued

Publications:
Burns CC, et al. PMID 16537593

Licensing Contact:
Karen Surabian, J.D., M.B.A.
Email: karen.surabian@nih.gov
Phone: 301-594-9719

OTT Reference No: E-328-2013-0
Updated: Jan 28, 2014