ndian subcontinent to Croatia and both DENV1 and
DENV2 from West Indies to France. But a very huge outbreak occurred in Madeira
in 2012-2013 reported to be due to DENV1 probably imported from Venezuela which
spread in other countries 43.
Dengue vaccine development and its challenges:
to unavailability of antiviral drugs and vaccine for dengue, fluid replacement
therapy in DSS, bed rest, care during critical phase remains to be the primary
supportive treatment for dengue. Dengue vaccine has been under the process of
development since 1940s but it has been challenged due to several factors like the complex pathophysiology of the
disease including mechanism that induced protective immunity against the
infection, the need to control all the four serotypes simultaneously to reduce
severity in both naive and previously immune individuals, lack of model
organism that can elucidates the pathogenesis, immune response and clinical
course of dengue infection and lack of investment10.
vaccine of dengue should provide lifelong protection against all the four
serotypes, it must be less reactive, safe, cheap and should be evaluated in
those population where we have full knowledge of all the serotypes circulation
and transmission 9 10. Candidates
for dengue vaccine development nowadays include live attenuated viruses,
inactivated viruses, subunit vaccines, DNA vaccines, cloned engineered viruses
and chimeric viruses using yellow fever vaccine and attenuated dengue viruses
as a backbone 9.
first ever DENV vaccine CYD-TDV, a recombinant chimeric vaccine developed by
Sanofi Pasteur has been licensed in 2015 in dengue-endemic countries like
Brazil, Costa Rica, El Salvador, Mexico and Philippines for use in the person
aged 9-45 years. It is a chimera of the attenuated backbone of the YFV 17D with
viral envelope proteins premembrane (prM) and envelope (E) from the four DENV
serotypes 44. Although it showed significantly high efficacy in phase III clinical
trial, lower efficacy was observed in both DENV2 infected individual and person
with no history of dengue infection. Further, it does not elicit maximum
adaptive immune responses that limit its uses, however, another alternative
chimeric vaccine is undergoing clinical trial that has the ability for broader
immune responses. Also, WHO recommends that vaccines should be implemented in
those regions that experience a high rate of dengue infection 45.
types of vaccine candidates are in different phase of the clinical trial which
shows that dengue vaccine development is in progress. Since the disease differs
epidemiologically with age, exposure to DENV at the time of vaccination, the
efficiency of the vaccine candidates differs and yield varying results.
Discovery of a new serotype has also complicated the disease. Close monitoring
of the disease is necessary to generate detailed epidemiological data in
different regions before the introduction of dengue vaccine 4644.
active research on antiviral candidates is also underway most of them have
failed to reach the phase of clinical trials due to many constraints.
Candidates like chloroquine, prednisolone, celgosivir, and lovastatin after
clinical trials have failed to meet the desired beneficial effects on the
defined clinical manifestation of dengue infection with exception of two other
candidates namely vermectin and ketotifen which is undergoing clinical trials.
Besides these, peptides due to its high specificity and selectivity are being
researched as a candidate for developing anti-DENV therapeutics 47.
WHO and Pediatric Dengue Vaccine Initiative (PDVI) in collaboration with
vaccine manufacturers and National Regulatory bodies have been working together
to accelerate dengue vaccine development 46. Despite several challenges,
dengue vaccine development has progressed in recent years 45.
has posed a major public health challenge, being one of the world’s most
important rapidly establishing disease. Most countries have become endemic to
dengue so proper management and supervision is needed to respond to dengue
outbreaks in future. In India, studies on all aspects of dengue at National
level is lacking which limits the power to estimate true burden of dengue.
studies on the serotype
in India as well as at international level both during and at the time of
epidemics will provide us insights on predicting dengue epidemics as mentioned
that in most of the countries dengue occurs every three to five years on a
cyclical pattern. It will help us in controlling the emerging virus and its
management in future outbreaks which will ultimately reduce morbidity and