DEVELOPMENT OF A TETRAVALENT DENGUE VACCINE: GUARDRAILS NEEDED

Illness caused by one of the four serotypes of dengue virus (DENV 1-4) is the leading cause of vector-borne disease globally, and 40% of the world's population is at risk. Vaccine development for dengue is complicated by the recognition that the serotype causing an individual's first infection with dengue virus may cause development of non-neutralizing antibodies, which can be associated with a more clinically severe second infection with a different serotype. This concept, antibody-dependent enhancement, has led the field to focus on development of vaccines that concurrently protect against all four serotypes (tetravalent). Three major groups have advanced the first generation of tetravalent dengue vaccines, with distinct formulations and approaches: Sanofi Pasteur, Takeda, and a collaborative academic team including University of Vermont, Johns Hopkins, and the National Institutes of Health. This review discusses the status of dengue vaccine development as well as the critical implications and consequences of dengue vaccine design and development.