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


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.

Potential Commercial Applications: Competitive Advantages:
  • 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
 
  • 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


Development Stage:
  • In vitro data available
  • In vivo data available (animal)


Inventors:

Gwong-Jen Chang (CDC)  ➽ more inventions...

Wayne Crill (CDC)  ➽ more inventions...

Holly Hughes (CDC)  ➽ more inventions...

Brent Davis (CDC)  ➽ more inventions...


Intellectual Property:
US Application No. 15/262,268
US Application No. 61/549,348
PCT Application No. PCT/US2012/060872
US Application No. 14/352,812
US Application No. 16/107,119

Publications:
Crill WD, et al. PMID 23162552

Licensing Contact:
Jeremiah Mitzelfelt,
Email: jeremiah.mitzelfelt@nih.gov
Phone: 301-443-8518

OTT Reference No: E-289-2013-0
Updated: Mar 18, 2014