Technology Bundle ID: TAB-2746

Vaccine Attenuation via Deoptimization of Synonymous Codons

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Licensing Contact:
Primary Inventors: 
Olen Kew (CDC)
Co-Inventors: 
Cara Burns (CDC), Jacueline Quay (CDC), Jing Shaw (CDC)
Development Stage: 
Pre-Clinical (in vitro)
Development Status: 

In vitro data available

Institute or Center: 
CDC

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.

Applications:
  • Vaccine design and development
  • Functional improvements for current vaccines
  • Increasing the phenotypic stability of live attenuated vaccines
  • Attenuation optimization endeavors
Advantages:
  • 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)

Patents

PCT Application PCT/US2005/036241
Filed on 2005-10-07
US Application 14/464,619
Filed on 2014-08-20
US Application 15/684,355
Filed on 2017-08-23
US Application 15/931,336
Filed on 2020-05-13
US Application 60/617,545
Filed on 2004-10-08
US Pat 10,695,414

Issued 2020-06-30
US Pat 8,846,051

Issued 2014-09-30

Various international patent applications pending or issued

Publications

Burns CC, et al.
PMID 16537593

Updated

Jan 28, 2014

Data Source: 
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