Dengue fever is a harmful virus that is transmitted through the bite of Aedes Aegypti mosquito. According to the World Health Organization, an approximate of 100 to 400 million infections occur each year.
A flavivirus causes dengue. There are four different, but closely related serotypes to this virus;
Recovery from infection from one serotype provides lifelong immunity against it. But, cross-immunity to the remaining serovar is only partial and temporary.
Thus, a person can be infected with three or probably all four dengue serotypes during their lifetime.
The same virus also causes dengue hemorrhagic fever (DHF), and it occurs when someone is bitten by the mosquito or exposed to blood infected with the virus.
Symptoms of dengue hemorrhagic fever (DHF) include:
- Blood spots on the skin
Despite the name, the criteria that differentiates DHF from dengue is not haemorrhaging, but a plasma leakage due to higher vascular permeability.
A dengue vaccine is considered to be the only solution for the disease in addition to other safety precautions like avoiding mosquito breeding. Vaccine activates the immune system and produces antibodies to fight the specific virus attack in the body.
Current status of development of dengue vaccine around the world
There is a need for significant preventive involvement against dengue to curb the disease.
An efficacious and safe vaccine against the four serotypes would significantly result in great control of the disease.
A vaccine for dengue will be a crucial tool to reach the goal set by WHO to reduce dengue morbidity by at least 25% and mortality by at least 50% by 2020.
As the disease continues to persist globally, there is an increased interest and support from researchers for vaccine development.
Developing a dengue vaccine is not an easy task because all four serotypes require equal levels of constriction.
There are a few vaccine candidates under progress, 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 trials. The other vaccine candidates have been tested in preclinical animal models or are being prepared for clinical trials.
For the efficiency of dengue vaccines, immunopathogenic complications such as antibody-mediated enhancement and autoimmunity of dengue disease need to be considered.
A live attenuated vaccine, chimeric yellow fever 17D—tetravalent dengue vaccine (CYD-TDV – Dengvaxia) developed by Sanofi Pasteur is the first licensed dengue vaccine in the world for clinical use.
Approval of the vaccine
The WHO Global Advisory Committee on Vaccine Safety (GACVS) last reviewed dengue vaccines in June 2015 and considered the Phase III clinical trial and long-term safety data of the tetravalent dengue vaccine Dengvaxia (CYD-TDV).
The U.S. Food and Drug Administration (FDA) approved Dengvaxia for the prevention of dengue disease caused by all serotypes.
It is the first treatment designed to protect against the deadly mosquito-borne virus.
The use of the vaccine is approved under certain conditions. Only children aged nine to sixteen, who have previously confirmed infections and who live in endemic areas, may receive the dose.
The vaccine is available internationally and has been extensively tested in over 40,000 people across 15 different countries.
There are still several other dengue vaccine candidates that are currently under different stages of development in various countries:
- DENVax – Also known as TAK-003, DEN-Vax was developed in Japan. It is a recombinant chimeric vaccine.
- TV003 – Also known as TetraVax-DV, is a tetravalent admixture of monovalent vaccines. The monovalent vaccines were tested separately.
- TDEN PIV – A tetravalent dengue purified inactivated vaccine, in phase 1 developmental trials. It is the product of collaboration between GSK and Walter Reed Army Institute of Research.
What is Dengvaxia (CYD- TDV)?
Dengvaxia (CYD-TDV) is the first dengue vaccine to be licensed. It was first licensed in Mexico for the use of individuals aged 9 to 45 living in endemic areas.
It is a live attenuated tetravalent chimeric vaccine made using recombinant DNA innovation. The vaccine is created by replacing the PrM (pre-membrane) and E (envelope) structural genes of yellow fever attenuated 17D strain vaccine with those from the four dengue serotypes.
It is given as three separate injections with six months intervals.
Dengvaxia has so far been adopted in 7 other dengue-endemic countries, namely, Peru, Paraguay, Brazil, El Salvador, Singapore, Costa Rica and Guatemala.
The vaccine has been shown to prevent severe dengue symptoms and reduce dengue-related hospitalisations by 80% cases.
Dengvaxia is currently in the mix of a profound debate because of the deaths of 10 children in the Philippines, related to the vaccine.
WHO Strategic Advisory Group of Experts (SAGE) on Immunisation recommended that Dengvaxia should only be given to those who have previously contacted the dengue virus infection.
SAGE further stated that it is risky to give the vaccine to individuals who have never been exposed to the virus.
How does the dengue vaccine work?
The vaccine must only be given to people who have been previously tested positive for the virus. The vaccine is provided under the skin and preferably in the upper arm.
Dengvaxia can only be acquired with a prescription and should be used according to official recommendations.
Vaccines work by ‘teaching’ the immune system how to defend the body against viruses.
The Dengvaxia contains weakened viruses that do not cause disease, and it works by triggering an immune response against all the four serotypes dengue viruses.
When a person is given the vaccine, the immune system differentiates the dengue proteins from the weakened viruses as ‘foreign’ and makes antibodies against them.
These antibodies then work to fight the virus while also developing a cellular memory which helps them to naturally create an immune response if more dengue attacks happen in future.
How long does Dengvaxia stay in the human system?
Dengvaxia has been shown in clinical trials to be effective and safe in those who have previously had the dengue virus.
But there is an increased risk of dengue getting worse in those who have only experienced their first natural dengue infection after vaccination (seronegative individuals).
The vaccine has four components, encoding for antigens of the four dengue virus strains.
At the point when an individual is given the vaccine, the immune system perceives the foreign pathogen that is present in the weakened viruses and creates antibodies against them.
This immunity protects the person from re-contacting the dengue virus. But, as stated above, it is more effective on those who have initially gotten dengue compared to those who never have.
This indicates that the effect of Dengvaxia and how long it stays in the human body varies from case to case. For some, it could last in the system for a few years and for others, it could stay effective all their life.
Long term safety of dengue vaccine
Usually, a vaccine helps trigger the creation of antibodies by the immune system. Then the antibodies work to fight against the virus when an infection occurs. However, Dengvaxia does not work this way.
The antibodies carry the virus to the whole body and help it to spread. The body produces antibodies against the vaccine, which means that Dengxavia is similar to the first infection for those who have not previously come into contact with the dengue virus.
According to Sanofi, the vaccine increases hospitalisation after a dengue infection from 1.1% to 1.6%. While this seems like a small risk, it means that an estimated 1,000 out of 1,000,000 children will be hospitalised because of the vaccine.
The overall population-level benefit of vaccination remains favourable, but the vaccine performs differently in seropositive (positive presence of the virus) versus seronegative (negative presence of the virus) individuals.
- Vaccine efficacy (VE) against virologically confirmed dengue was high among baseline seropositive participants above nine years old but much lower among baseline seronegative participants in the first 25 months after the first dose of vaccine.
- There is an increased risk of hospitalisation and severe dengue in seronegative individuals starting about 30 months after the first dose.
- In areas of 70% dengue seroprevalence:
- Over a 5-year follow-up, for every four severe cases prevented in seropositive, there would be one excess severe case in seronegative per 1,000 vaccines.
- For every 13 Hospitalisations prevented in seropositive vaccines, there would be one excess hospitalisation in seronegative vaccines per 1,000 vaccines.
Just like every other vaccine or medication, Dengvaxia has several side effects which include:
- Injection area reactions (pain, redness, swelling)
- Muscle pain
WHO considers dengue to be one of the fastest spreading arboviral diseases. An efficacious vaccine will help lower the number of cases. The only available WHO-approved dengue vaccine to date is Dengvaxia. It is a live weakened tetravalent vaccine made using recombinant DNA technology.
As mentioned in the article, the duration that Dengvaxia lasts in a human body varies from one individual to the other. However, with the advancements in medical technology and extensive clinical trials happening all around the world, we can look forward to more effective versions of dengue vaccine in the times to come.