Hawaii Biotech are in Phase 1 trials of a monovalent Dengue-1 vaccine consisting of envelope proteins expressed by an insect cell system. With successful results, this vaccine will next progress to tetravalent trials. The CDC vaccine has been licenced to Inviragen for clinical trials towards a tetravalent vaccine due to begin shortly The clinical trial program is becoming typical of dengue vaccine development with initial trials in dengue-free countries, in this case USA, before Inviragen moves to Singapore for later phase clinical trials in an endemic area.
The other feature of this dengue vaccine development program and the vaccines discussed here is the partnership with significant biotech companies able to scale vaccine development to the levels that will be necessary to supply the world with dengue vaccines when they do become available. Australia remains on the list of countries in which dengue vaccines are likely to be licensed early due to the quality of research and regulation, the presence of endemic dengue and the proximity to hyperendemic countries.
Submit your article In Australia this year, outbreaks have been declared in Tully February and Townsville April , both of which have been Dengue 2 infections 5 Despite a number of episodes transiently reducing international travel, the increase in global dengue is related to increased mobility of populations.
Progress towards a Dengue Vaccine The conventional wisdom is that a tetravalent vaccine will be necessary to avoid heterotypic reactions to serotypes against which only marginal immunity is held 8.
Author Information. References 1. The epidemiology of dengue in the Americas over the last three decades: A worrisome reality. Am J Trop Med Hyg ; 82 1 : Jelinek T. Trends in the epidemiology of dengue fever and their relevance for importation to Europe. Available at www. Kitchener SJ. The development of dengue vaccines and their military significance.
Aust Mil Med ; 9 2 : Serological testing, clinical incidence and serosurveillance of dengue in the Australian Defence Force, East Timor. Arbo Res Aust ; 8: Importation of dengue by soldiers returning from East Timor to north Queensland, Australia. J Trav Med ; 9: Halstead SB. In the absence of subgroups within the seronegative vaccinated population for identifying immune correlates, we compared Ab responses in individuals exposed to primary DENV1 and DENV3 infections and individuals who were vaccinated to identify improved correlates.
Therefore, the presence of TS NAbs alone may not always be sufficient for protection. TS NAbs may have to be maintained above a certain threshold for protection.
Individuals with TS NAb responses may be susceptible to infections caused by natural variant strains that differ at critical TS Ab epitopes from the vaccine strain. Dengvaxia was efficacious in children with preexisting immunity to DENVs who were vaccinated, and our study was not designed to identify vaccine correlates and mechanisms of protection in this population.
Detailed Methods appear in Supplemental Methods. The collection, storage, and use of these samples for research has been approved by the Institutional Review Board of the University of North Carolina at Chapel Hill protocol MB helped with the initial characterization and selection of clinical samples for this study.
CA and SH conducted experiments and wrote the first drafts of the manuscript. All the authors provided critical edits. Reference information: J Clin Invest.
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Sandra Henein: ude. Moser: moc. Phone: Authorship note: SH and CA contributed equally to this work. Received Dec 21; Accepted May Associated Data Supplementary Materials Supplemental data. Keywords: Vaccines, Virology. Keywords: Adaptive immunity, Immunoglobulins. Introduction The 4 dengue virus serotypes DENV1—4 are mosquito-transmitted flaviviruses estimated to infect over million people every year. Open in a separate window.
Figure 1. Figure 2. Figure 3. Dengue vaccine responses in the general population of children who were seronegative at baseline.
Figure 4. Methods Detailed Methods appear in Supplemental Methods. Study approval. Author contributions MB helped with the initial characterization and selection of clinical samples for this study.
Supplementary Material Supplemental data: Click here to view. Version Changes Version 1. Version 2. The major clinical manifestations of severe DENV disease are vascular leakage, thrombocytopenia, and hemorrhage, yet the detailed mechanisms are not fully resolved. Besides the direct effects of the virus, immunopathological aspects are also involved in the development of dengue symptoms. Although no licensed dengue vaccine is yet available, several vaccine candidates are under development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, and live recombinant, DNA and subunit vaccines.
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