New Delhi: A dengue vaccine could be one of the first to benefit from a government decision that allows certain drugs and vaccines approved in specified countries to be launched in India without clinical trials. The vaccine, QDenga, is manufactured by Japanese pharmaceutical firm Takeda.
Last year, the World Health Organisation (WHO) had recommended QDenga for use in endemic countries. But in India, the Central Drugs Standard Control Organisation (CDSCO) had earlier this year approved a proposal to conduct a phase 3 trial of QDenga to prove its safety and efficacy in the Indian population.
On 7 August, the CDSCO issued an order which said that under rule 101 of the New Drugs and Clinical Trial Rules, 2019, the central government has waived local clinical trials for the approval of new drugs.
A Takeda spokesperson told ThePrint, “We are currently in discussions with the Indian regulator for appropriate regulatory approvals and will launch the vaccine post receipt of approval by Indian health authorities, in compliance with all regulatory requirements of the country.”
If that happens, it will be a significant boost for India’s fight against dengue, which featured in the WHO’s 2019 list of top 10 threats to global health, and is a major public health burden in India.
Even though QDenga is being seen as a promising preventive tool against all four strains of dengue, lack of robust evidence to support this makes some scientists sceptical. They say that a vaccine being developed at the US National Institutes of Health (NIH) by Indian companies may be more useful for the country setting where all four strains are in circulation.
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What causes dengue, and its burden in India
Dengue is caused by any of four dengue virus (DENV) serotypes (DENV 1 to 4), each of which can cause dengue fever or severe dengue. It is mainly spread by mosquito species Aedes aegypti. India, over the last few years, has seen an alarming rise in the number of dengue-related cases, hospitalisations and deaths.
Till June this year, even before the peak dengue season, India had registered 32,091 dengue cases and 32 deaths. The dengue cases till June were 75 percent higher than those recorded in the corresponding period last year.
India is among the top 30 countries with the highest burden of dengue globally. According to government estimates, among the 20 to 25 percent of cases where dengue symptoms are clinically apparent, children are at a significantly higher risk of hospitalisation and mortality.
Top virologist Dr Gagandeep Kang explained to ThePrint that dengue can be anything from an infection without symptoms, a mild fever or a severe fever with musculoskeletal pain to haemorrhagic fever (low platelets leading to bleeding) and dengue shock syndrome (severe form of dengue infection that can lead to circulatory collapse).
“The latter two can be very severe and result in death if not recognised and treated early. These two conditions usually happen, not in the first but in subsequent infection, when the dengue virus strain is different from the one that caused the earlier infection,” she said.
Now, there is a beacon of hope against the disease.
As the dengue-related crisis grows in the country, there are some vaccines against it in the pipeline that are ready to be available for use for people in the near future. But specialists stress that any vaccine against the viral disease must overcome two major challenges.
“The first challenge is that the vaccine should be able to trigger a balanced immune response against all four DENV serotypes,” scientist and virologist Dr Shahid Jameel, a fellow at Green Templeton College, University of Oxford, and a visiting professor at Ashoka University, told ThePrint.
“The second challenge is that a suboptimal immune response can enhance the infection by allowing the virus to better enter its primary target cells — macrophages. This is called antibody-dependent enhancement (ADE),” Dr Jameel added.
ThePrint takes a look at the currently available and upcoming dengue vaccines, and whether they have the potential to tackle the dual challenge.
Dengvaxia, its controversies, and how it’s administered
Dengvaxia is the first global dengue vaccine. Manufactured by French vaccine major Sanofi, it is a recombinant yellow fever virus-based attenuated dengue vaccine. This means that a live or weakened virus strain has been altered so that it cannot cause disease. Since 2015, it has been approved in 20 countries, including the United States and Europe, for use in individuals above the age of nine years.
However, this vaccine, which was initially approved also for dengue naive individuals (those without prior infection), became embroiled in a massive controversy following reports of deaths of several children due to severe dengue after a government initiated mass vaccination of school children in the Philippines in 2017.
“There was a low immunisation rate, and a loss of confidence in vaccines was seen later was due to the Philippines controversy,” Dr Ashwani Kumar, former director of the Indian Council of Medical Research-Vector Control Research Centre (ICMR-VCRC), told ThePrint.
Kang explained that vaccines for dengue should be given to people who have had at least one dengue infection previously because if they are given to someone who has never had dengue, the body may treat the vaccination as the first infection, and when a real first infection happens, the body’s immune system may react as if it is a second infection. This may result in severe disease.
Dengvaxia is given in three doses, six months apart, to those living in dengue endemic countries. The vaccine has shown an efficacy of 56.5 percent against asymptomatic dengue and 60.8 percent against symptomatic dengue.
Since 2018, however, for fear of ADE, this vaccine is recommended only for those who already had a prior dengue infection, and not to people who never had a dengue infection.
“This means additional testing is required to ensure that the recipient already has antibodies to the dengue virus. For this reason, it is not being used widely,” Dr Jameel pointed out.
A Sanofi spokesperson told ThePrint that the company has made the decision to discontinue Dengvaxia from the third quarter of 2026 due to low global demand for this product and has no plan to launch the vaccine in India.
“This decision is not driven by quality, safety or efficacy concerns,” the company said.
“While we have made consistent efforts to facilitate its access and the implementation of the ‘Screen & Vaccinate’ (S&V) approach as recommended by the WHO in 2018, uptake and demand has remained low. Despite an increased prevalence of dengue in different parts of the world, there’s only one Dengvaxia immunisation program in place due to the complexity of implementing this product,” the company added.
“In view of the above decision, we will not pursue the registration of Dengvaxia any further in India,” the company spokesperson added. This hinted at the fact that the company was earlier considering the launch of the vaccine in the country.
QDenga, a vaccine with ‘genetic backbone’ for all 4 serotypes
QDenga consists of live-attenuated dengue serotype 2 virus (DENV2), which provides the genetic “backbone” for all four dengue virus serotypes, and is designed to help protect against any of these serotypes. This means that the virus inside the vaccine is alive, but its virulence is reduced.
In the European Union, the vaccine is indicated for the prevention of dengue disease in individuals of four years of age and above, and should be given in two doses, with a gap of three months between them.
This vaccine has shown around 80.2 percent efficacy against dengue caused by any serotype at the time of primary analysis, but it has been found to decline over time, with 62 percent efficacy at 3 years and 61.2 percent efficacy at 4.5 years.
“This vaccine has shown to have over 80 percent protection which is considered high. It causes mild fever, lethargy and may cause a rash or make the point of injection a bit sore — but these get resolved in a day or two,” Kumar said.
The vaccine is currently available for children and adults in the private market in countries like Europe, Indonesia and Thailand, and is part of private and some public programmes in Argentina and Brazil.
Dr Jameel highlighted that since the vaccine uses a DENV2 backbone, the lack of an efficacy-risk profile for ADE against serotypes DENV3 and DENV4 does not allow for the vaccine’s use in low endemic countries.
NIH vaccine under clinical trials in India
A dengue vaccine is in the late stages of clinical development at the US National Institutes of Health. This vaccine is expected to be effective against all four serotypes.
Under the Indo-US Vaccine Action Programme, this vaccine has been licensed to three Indian companies — Panacea Biotec, Serum Institute of India (SII) and Indian Immunologicals.
New Delhi-based Panacea and Pune-based SII have used the same active ingredient developed by the NIH but inactive ingredients are different.
Dr Jameel said that this vaccine has proven safe and effective against DENV1 and DENV2 in about 20,000 people in Brazil but could not be tested against DENV3 and DENV4.
A large outbreak of DENV3 in Brazil this year offers that opportunity, he said, adding that since India has seen the circulation of all four dengue virus serotypes, none of the available vaccines have so far proven useful for our setting.
“India needs to set up clinical cohorts, testing sites and bioassay labs to carry out phase 3 trials of the NIH vaccine, which can be manufactured in the country,” Dr Jameel stressed.
Sources in SII told ThePrint that phase 1 study of Dengusiil vaccine (the name given by the SII to the vaccine candidate) has been completed in Australia and India as well.
“Phase 1 study in adults is also completed and we have recruited children of younger age for the trials, which will be over soon, post which we will prepare for phase 3 trials of the vaccine” a high-ranking source in the SII told ThePrint.
The vaccine is likely to be rolled out in the market by 2027, if clinical trials are completed with timely approvals, the company sources added.
For the clinical trial of Panacea’s vaccine candidate, named DengiAll, the firm has tied up with the Indian Council of Medical Research (ICMR).
This vaccine has now started a large-scale phase 3 trial on over 10,000 participants aged 18-60 years across 19 sites in the country.
Indian Immunologicals, a fully-owned subsidiary of the National Dairy Development Board, and a Hyderabad-based firm, did not respond to a query on the status of its dengue vaccine candidate. This report will be updated if and when a response is received.
But sources in the company told ThePrint that it is about to start phases 2 and 3 of the clinical trials of the vaccine and is looking at a 2026 timeline to commercially launch the vaccine in the country.
(Edited by Radifah Kabir)
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