Technology Bundle ID: TAB-2794

Dengue Vaccines: Tools for Redirecting the Immune Response for Safe, Efficacious Dengue Vaccination

Request More Info
Licensing Contact:
Primary Inventors: 
Gwong-Jen Chang (CDC)
Co-Inventors: 
Brent Davis (CDC), Holly Hughes (CDC), Wayne Crill (CDC)
Development Stage: 
Pre-clinical (in vivo)
Development Status: 
  • In vitro data available
  • In vivo data available (animal)
Institute or Center: 
CDC

This CDC-developed invention relates to dengue vaccines that have been specifically developed for improved efficacy and directed immune response to avoid antibody-dependent enhancement (ADE) safety issues that, theoretically, may be associated with dengue vaccines and vaccinations. Dengue viral infection typically causes a debilitating but non-lethal illness in hosts. However, dengue hemorrhagic fever (DHF), the much more severe and life-threatening condition, is generally attributed to secondary dengue infections caused by a serotype different from the initial infection serotype by way of ADE. This effect, particularly notable in dengue viruses, should be given special consideration during vaccine design and construction.

This in vivo-validated technology provides a strategy and mechanism for increasing the safety of dengue vaccines and diminishing the likelihood of such vaccines inadvertently harming a recipient due to ADE-mediated effects. Any safe, effective dengue vaccine must produce well-balanced and tetravalent (for all four dengue serotypes) protective immunity. Despite decades of investigative effort there remains no effective, commercially available dengue vaccine and the greatest hurdle has been the difficulty of rapidly inducing this balanced immunity to all four dengue serotypes.

With this invention, CDC researchers have developed a cross-reactivity reduced dengue serotype 1 (DENV-1) DNA vaccine engineered to directly address ADE-related vaccine safety concerns. In vivo murine testing of wild-type and cross-reactivity-reduced vaccines demonstrated that this theoretical vaccine safety concern is real and that the cross-reactivity reduced DNA vaccine dramatically reduces dengue vaccination safety risk while increasing protective antibody responses. Properly developed and implemented, this novel vaccination strategy should help overcome this previously-unaddressed hindrance to dengue vaccine development.

Applications:
  • Creation of a safe, efficacious and well-balanced dengue virus vaccine
  • Improving currently developed/developing dengue vaccines to mitigate potential antibody-dependent enhancement safety issues
  • Research tools for vaccine development programs for other flaviviruses, HIV
Advantages:
  • Murine in vivo studies indicating proof-of-principle, safety and efficacy
  • Addresses a long-standing “serotype immunity balancing” issue for dengue vaccine development
  • Presently there are no safe, effective commercially available dengue vaccines

Patents

PCT Application PCT/US2012/060872
Filed on 2012-10-18
US Application 14/352,812
Filed on 2014-04-18
US Application 16/745,986
Filed on 2020-01-17
US Application 61/549,348
Filed on 2011-10-20
US Pat 10,092,637

Issued 2018-10-09
US Pat 10,568,956

Issued 2020-02-25

Publications

Crill WD, et al.
PMID 23162552

Updated

Mar 18, 2014

Data Source: 
tts