A dengue vaccine is considered to be an excellent solution to prevent and protect people at risk from the virus.
The first licensed dengue vaccine is Dengvaxia (CYD-TDV). It is a live attenuated tetravalent chimeric vaccine made using recombinant DNA innovation. It is given in three different dosages with six months intervals.
WHO Strategic Advisory Group of Experts (SAGE) on Immunisation recommended that Dengvaxia should only be given to those who have a history of dengue virus infection.
Takeda Pharmaceutical Company Limited is a research-based global company that is striving towards better health for patients worldwide through leading innovation in medicine.
Takeda’s dengue vaccine, TAK-003 is being developed to protect the population at risk for dengue across geographies without having to consider previous exposure to the virus.
What is the Takeda dengue vaccine?
Takeda is a pharmaceutical company that works towards better health for patients through research. Their ethical drugs are marketed to around 100 countries worldwide.
Takeda’s TAK-003 is a vaccine intended to secure against all four types of the dengue virus and initiate different arms of the immune system, including antibodies and immune cells.
It live-attenuated dengue serotype two virus (DENV-2), which provides the genetic ‘backbone’ for all four vaccine viruses.
Since TAK-003 is based on an attenuated form of the dengue virus itself, it exposes the individual to several components of the virus, which could be significant in protection against future infection with the virus.
Studies and clinical trials on Takeda dengue vaccine (TAK-003)
Takeda’s live-attenuated tetravalent dengue vaccine candidate, TAK-003, is being studied in healthy children and adults from dengue-endemic and non endemic countries. Its clinical trial consists of five Phase 3 trials.
DEN-301 is a Phase 3 trial to protect people against dengue fever and to look at long-term safety results. This study will look at the success rate of TAK-003 in preventing dengue fever (vaccine efficacy) and long-term side effects of the vaccine.
DEN-304 is a Phase 3 trial to investigate lot-to-lot consistency in terms of equivalence of the immune responses induced by 3 consecutive lots of TAK-003 in healthy participants in non-endemic countries for dengue.
DEN-305 is a Phase 3 trial in which TAK-003 will be tested in sequential administration of yellow fever (YF-17D) vaccine to assess immunogenicity and safety in healthy adult participants in non-endemic areas for both dengue and yellow fever.
DEN-314 is a Phase 3 trial in which TAK-003 will be co-administered with hepatitis A virus (HAV) vaccine to assess immunogenicity and safety in healthy participants in non-endemic areas for dengue and HAV.
DEN-315 is a Phase 3 trial tested to assess the safety and immunogenicity in healthy adolescents in non-endemic area(s) for dengue.
TAK-003 Dengue Vaccine Indication and dosage
TAK-003 is indicated for the prevention of the Dengue virus brought by any of the four Dengue serotypes. Dengue is the quickest spreading mosquito-borne viral disease and is one of the World Health Organization’s top 10 dangers to global health in 2019.
TAK-003 is the second dengue vaccine to enter clinical trials, after Sanofi Pasteur’s Dengvaxia. Sanofi’s vaccine was 56% to 61% effective in preventing dengue in children, but it was dangerous to those who never contracted the virus before the vaccine.
Takeda’s TAK-003 is based on a dengue two virus, with genes from the remaining three dengue viruses. Dengvaxia is based on a yellow fever virus with dengue genes added. Takeda hopes the all-dengue design will trigger a more robust immune response.
In a phase 2 study, TAK-003 was given as a single DV 0.5 mL subcutaneous injection on Day 1 and Day 90 in the clinical trial. The onset of protection was seen after the 1st dose, with 81% VE between the 1st and 2nd doses.
Efficacy and long term safety of Takeda dengue vaccine
Phase 1 and Phase 2 clinical trial programs for TAK-003 consists of eight studies in children and adolescents. The information produced from these studies supported progression into a Phase 3 study.
Safety data from an 18-month interval showed that TAK-003 instigated immune responses against all four dengue serotypes, in both seropositive and seronegative participants and the vaccine was discovered to be generally safe and well-tolerated.
In a study called Tetravalent Immunization against Dengue Efficacy Study (Tides), investigators assessed the Takeda vaccine, TAK-003, against placebo in more than 20,000 participants aged four to 16 in dengue-endemic nations of Latin America and Asia. Twice as many participants received the vaccine as those who received placebo.
The vaccine efficacy was 80.2% in the 12 months after the 2nd vaccine dose, which was administered 3-months after the 1st dose.
Notably, efficiency differed among dengue serotypes. The vaccine was 73.7% effective against dengue serotype 1, 97.7% effective against serotype 2 and 62.6% effective against serotype 3. The investigators didn’t follow enough serotype 4 cases to reach viability.
The shot was 95.4% effective in preventing dengue that required hospitalisation. There were five hospitalisations in the vaccine group versus 53 in the placebo group.
The Lancet published an article on safety and immunogenicity of a tetravalent dengue vaccine in healthy participants aged two to 17 years at three sites in the Dominican Republic, Panama, and the Philippines.
A randomised, placebo-controlled, phase 2 trial, which concluded saying TAK-003 elicited antibody responses against all four serotypes, which persisted to 48 months post-vaccination, regardless of baseline serostatus.
Recently on July 13, 2020, the long-term safety and immune response of TAK-003 in children and adults were studied. At month 36, seropositivity rates were:
- DENV-1: 97.3%
- DENV-2: 98.7%
- DENV-3: 88.0%
- DENV-4: 56.0%
The TAK-003 vaccine is not currently licensed anywhere in the world.
Latest news and updates on TAK-003
November 5, 2020 – Reuters reported ‘Takeda’s dengue vaccine candidate, TAK-003, is on track for regulatory filing in Asia, Latin America, and the European Union by the end of fiscal 2020.
July 13, 2020 – The phase 2 trial demonstrated persistence of neutralising antibody titers against TAK-003 for over three years in children and adults living in dengue-endemic countries, with limited contribution from natural infection. TAK-003 was well tolerated.
March 17, 2020 – The Lancet published the ‘Safety and immunogenicity of TAK-003 in children aged 2–17 years: a randomised, placebo-controlled, phase 2 trial.
If approved, Takeda’s shot would follow Sanofi’s Dengvaxia onto the market. The French drugmaker launched the product in 2016. However, its endeavour has failed to satisfy expectations because of a safety controversy that tripped up the rollout.
In 2017, the company said a new analysis found that the vaccine could cause more severe disease in those who have never contracted the virus.
Although long-term data are needed to assess the safety and efficacy of Takeda’s vaccine candidate fully, the outcome from Phase 3 study indicates that TAK-003 has chances of being an essential tool in preventing dengue.
The Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial is being continuously monitored. The safety and efficacy will be evaluated in a total of four and a half years.