Disease Information

Photo courtesey of Dr. Richard Kuhn, Purdue University

The dengue viruses are endemic throughout the world's subtropical and tropical regions, threatening over 2.5 billion people. Infection is caused by one of four different RNA viruses: dengue type 1 (DEN-1), DEN-2, DEN-3, DEN-4. For a dengue vaccine to be safe and effective, it must be capable of neutralizing all four of the dengue viruses.

Inviragen has exclusively licensed a promising dengue vaccine developed at the Centers for Disease Control and Prevention (CDC). The CDC scientists started with a virus backbone that is a weakened or attenuated DEN-2 virus, strain PDK-53. This DEN-2 vaccine was previously shown to be safe and generate long-lasting immune responses in Phase 1 clinical trials.

The vaccines for the remaining three dengue viruses were engineered by replacing the DEN-2 PDK-53 structural genes (prM and E) with the prM (premembrane) and E (envelope) genes of DEN-1, DEN-3, or DEN-4 (see figure below; C = capsid protein gene, NS = nonstructural protein gene, 5'/3'-terminal shaded boxes = untranslated regions of the viral RNA genome). This method created hybrid (chimeric) viruses that express the prM and E surface antigens of DEN-1, DEN-3, or DEN-4, while retaining the genetic alterations responsible for the safety of the original DEN-2 vaccine (red triangles in figure below).

In preclinical testing, the chimeric DEN-2/1, DEN-2/3, and DEN-2/4 vaccine viruses retained the safety properties of the original DEN-2 PDK-53 vaccine, including growth characteristics in cell culture and safety in animal models. Each chimera also generated potent immune responses against the correct dengue virus.

DENVax is a tetravalent (four-component) combination vaccine containing the original attenuated DEN-2 PDK-53 vaccine and each of the chimeric vaccines (DEN-2/1, DEN-2/3 and DEN-2/4). In DENVax, all four of the components contain the same, identical safety mutations. Thus, the safety of DENVax can be assured by sensitive genetic tests throughout its manufacture. In addition, the possibility of generating a pathogenic strain by recombinantion between the vaccines is eliminated. These are distinct advantages over competitive dengue vaccine technologies.

DENVax generated antibody responses that could neutralize all four dengue viruses in animal models. Preliminary data indicates that this tetravalent DEN vaccine candidate is safe and immunogenic in non-human primates.

With its global partners, Inviragen is preparing DENVax for human clinical trials. A safe, affordable and effective vaccine that can neutralize all four dengue viruses will have tremendous impact on global health.