Abstract
Dengue is one of the most important emerging vector-borne viral diseases. There are four serotypes of dengue viruses (DENV), each of which is capable of causing self-limited dengue fever (DF) or even life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). 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. The live attenuated virus vaccines and live chimeric virus vaccines are undergoing clinical evaluation. The other vaccine candidates have been evaluated in preclinical animal models or are being prepared for clinical trials. For the safety and efficacy of dengue vaccines, the immunopathogenic complications such as antibody-mediated enhancement and autoimmunity of dengue disease need to be considered.
Highlights
Dengue virus (DENV) is a member of the Flavivirus genus of the Flaviviriade family which includes yellow fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and tick-borne encephalitis virus
Current vaccine progress no licensed dengue vaccine is yet available, several vaccine candidates are under development
Phase II study showed only 30 percent effectiveness and efficacies against only DENV1, 3 and 4 serotypes [115]. These results indicate that the Sanofi dengue vaccine still carries the risk of Antibody-dependent enhancement (ADE) and needs more testing, modification and/or clinical trials especially in dengue-endemic countries [116]
Summary
Dengue virus (DENV) is a member of the Flavivirus genus of the Flaviviriade family which includes yellow fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and tick-borne encephalitis virus. Phase II study showed only 30 percent effectiveness and efficacies against only DENV1, 3 and 4 serotypes [115] These results indicate that the Sanofi dengue vaccine still carries the risk of ADE and needs more testing, modification and/or clinical trials especially in dengue-endemic countries [116]. Combining the tetravalent and adjuvant effects, a novel single-dose dengue subunit vaccine (lipocEDIII) was demonstrated to neutralize the four serotypes of DENV and induce memory immune responses [131]. Several studies indicated that passive immunization with anti-NS1 Abs [131], DNA vaccine against NS1 proteins [135,136,137,138], or recombinant vaccinia virus expressing NS1 [139] and active immunization with NS1 proteins [77,140] could provide protection in mice against DENV. The cross-protection against other serotypes needs to be further investigated
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