Development of a Dengue Vaccine in Humans: So Near, Yet So Far
نویسندگان
چکیده
Due to a combination of favourable factors promoting the population growth and geographical spread of the Aedes mosquito vector of dengue, the incidence of this rapidly emerging tropical infectious disease has increased over 30-fold in less than half a century. Today, there are around 100 million reported clinical cases each year. Co-circulation of multiple serotypes of the dengue virus causes a variety of manifestations ranging from mild symptoms, via debilitating morbidity, to a severe form that, although relatively rare, has a high mortality rate. As current dengue control programs are severely strained, an efficacious vaccine to prevent infection is an urgent global public health priority. However, production of a dengue vaccine is compromised by an incomplete understanding of compounding factors including the existence of five now known serotypes, duration of protection provided by vaccination, dosing regimen and period, cost of production, and determination of the immune status of vaccine recipients. All these issues need to be considered in successful vaccine design. Encouragingly, prior success with immunization strategies against the closely related viruses Japanese encephalitis and yellow fever provides a precedent to deliver a safe, effective and affordable dengue vaccine. At least seven candidates are presently in clinical trials. These preparations are based on: DNA; protein subunit; purified inactivated virus; classic live attenuated virus; live attenuated heterologous virus chimera; live attenuated homologous dengue chimera; live attenuated deletion mutation. Of these, CYD-TDV, the three-dose live recombinant tetravalent chimeric vaccine based on a backbone of the yellow fever 17D vaccine strain, has advanced furthest and it is hoped to soon be granted a commercial license.
منابع مشابه
Induction of Neutralizing Antibodies against Four Serotypes of Dengue Viruses by MixBiEDIII, a Tetravalent Dengue Vaccine
The worldwide expansion of four serotypes of dengue virus (DENV) poses great risk to global public health. Several vaccine candidates are under development. However, none is yet available for humans. In the present study, a novel strategy to produce tetravalent DENV vaccine based on envelope protein domain III (EDIII) was proposed. Tandem EDIIIs of two serotypes (type 1-2 and type 3-4) of DENV ...
متن کاملNeutralizing Antibody Response and Efficacy of Novel Recombinant Tetravalent Dengue DNA Vaccine Comprising Envelope Domain III in Mice
Background: Dengue is a global arboviral threat to humans; causing 390 million infections per year. The availability of safe and effective tetravalent dengue vaccine is a global requirement to prevent epidemics, morbidity, and mortality associated with it. Methods: Five experimental groups (6 mice per group) each of 5-week-old BALB/c mice were immunized with vaccine and placebo (empty plasmid) ...
متن کاملThe Complexity of a Dengue Vaccine: A Review of the Human Antibody Response
Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have be...
متن کاملWild dengue virus types 1, 2 and 3 viremia in rhesus monkeys.
Among the flaviviruses, dengue, with its four serotypes, has spread throughout the tropics. The most advanced vaccines developed so far include live attenuated viruses, which have been tested in humans but none has been licensed. Preclinical testing of dengue vaccine candidates is performed initially in mice and in nonhuman primates. In the latter the main criteria used to assay protection are ...
متن کاملDengue Vaccines: Challenge and Confrontation
Dengue has been recognized as one of the most important vector-borne human diseases. The disease is induced by dengue virus infection resulting from the bite of an infected Aedes spp. mosquito after imbibing the tainted blood from animals or patients. Dynamic clinical spectrums ranging from asymptomatic, undifferentiated fever, typical dengue fever (DF), dengue hemorrhagic fever (DHF) and dengu...
متن کامل