Establishing a Dengue Controlled Human Infection Model in Viet Nam (360G-Wellcome-212345_Z_18_Z)

Dengue is a mosquito-borne viral infection of major global significance. Millions of infections occur annually encompassing a wide clinical spectrum from inapparent infection to severe and fatal disease. Infection can be caused by any of four related serotypes but second infections with a different serotype are more likely to be associated with severity than primary infections. Although the first dengue vaccine was recently licensed, efficacy was only moderate despite demonstration of neutralising antibody responses to all serotypes, and there are now major safety concerns regarding priming of naïve vaccinees for severe disease later. To evaluate alternative vaccine candidates, NIAID has identified two attenuated challenge viruses with excellent safety profiles in dengue controlled human infection models (Dengue- CHIM) in US adults. We plan to collaborate with this experienced group to establish a similar Dengue-CHIM in Vietnam. However, since this is the first application in an endemic setting and no legal/regulatory framework exists, we propose an initial phase focused on bioethics/stakeholder engagement to develop a suitable regulatory framework, before moving forward to explore crucial research questions. An endemic setting Dengue-CHIM has great potential to advance dengue vaccine development and address the role of dengue immunity in the protection and pathogenesis of natural infection.