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.