Abstract
Dengue virus (DENV) continues to spread globally and is a major cause of morbidity and mortality. Currently, there is no antiviral treatment to diminish severe illness or a vaccine to induce protection from infection. An effective dengue vaccine that protects against all four DENV serotypes is a high priority for endemic countries and several candidates are in development by various United States Federal Agencies and private pharmaceutical companies. Challenges faced by dengue vaccine developers include creating tetravalent formulations that provide tetravalent protection, the lack of a correlate of protective immunity, a changing viral landscape as DENV evolves, and a complex viral-host pathogenesis that can result in a spectrum of illness from subclinical infection to severe hemorrhagic fever. There have been a number of long-term prospective studies on DENV transmission and dengue severity that have provided invaluable information on DENV epidemiology and pathogenesis of this disease. In this section, we will review the critical lessons learned from these studies and their application for dengue vaccine development.
Highlights
The global dengue pandemic and its associated morbidity and mortality have been covered in other excellent reviews and sections of this textbook and will not be reviewed here
Prospective studies have been a valuable tool in understanding the epidemiology and pathogenesis of dengue virus (DENV) infection
For the dengue vaccine developer these studies offer the advantage of determining the true incidence of infection, the full spectrum of clinical outcomes from subclinical to severe hospitalized illness, risk factors for disease severity, and viral information on the genetics and evolution of DENV and its spatial and temporal spread
Summary
The global dengue pandemic and its associated morbidity and mortality have been covered in other excellent reviews and sections of this textbook and will not be reviewed here. The results of a Phase 2b candidate tetravalent DENV vaccine [yellow fever (YF)-dengue chimeric, Sanofi Pasteur] were published [1]. This was conducted in a highly flavivirus antibody experienced cohort of children in Thailand and demonstrated an excellent safety and neutralizing antibody immunogenicity profile. Efficacy varied by DENV type with the lowest noted against DENV-2 (9.2%), which was the predominant circulating DENV serotype at the time of the trial The results of this efficacy trial highlighted several development challenges for a dengue vaccine including the lack of a correlation of protection despite the detection of serotype-specific neutralizing antibody. The first prospective cohort study was conducted in Rayong, Thailand in January 1980 among children who were sampled from schools www.frontiersin.org
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
