In a significant collaborative effort, researchers from the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) and the Larner College of Medicine at the University of Vermont (UVM), USA, have initiated groundbreaking studies on a promising tetravalent dengue vaccine in dengue-endemic Bangladesh.
The research, which focused on evaluating the single-dose tetravalent dengue vaccine candidate TV005, showcased positive results in terms of safety and immune responsiveness across both children and adults.
Dengue, a mosquito-borne virus, poses an escalating global risk, particularly in tropical regions. The mild cases manifest as fever and bone pain, while severe cases are linked to shock, bleeding, and, at times, fatalities.
Bangladesh, with its dense population of approximately 170 million people, has experienced dengue outbreaks for over two decades, with the ongoing 2023 outbreak being the most severe on record. The country has witnessed an overwhelming number of hospitalisations and deaths due to dengue during this outbreak.
As part of the "Dengue in Dhaka Initiative (DIDI)" launched in 2015, icddr,b and UVM investigators embarked on the first-ever research on dengue vaccines in Bangladesh. The study, published in The Lancet Infectious Diseases, is a phase II randomized and controlled clinical trial that evaluated the safety, immunogenicity, and 3-year durability of the TV005 tetravalent live-attenuated dengue vaccine.
The study involved nearly 200 volunteers across four age cohorts (ages 1-49 years) who received either the TV005 vaccine or a placebo between 2016 and 2019. Notably, TV005 demonstrated excellent tolerance, eliciting antibodies for all four dengue serotypes, with no reported cases of dengue among vaccinated volunteers.
"Antibodies to all four dengue serotypes were found in most volunteers after vaccination; individuals who had been infected previously with dengue had higher antibody counts. Although the study was not designed to evaluate efficacy, no cases of dengue were detected in vaccinated volunteers. This data moves the TV005 dengue vaccine closer to widespread use in endemic populations while garnering support for ongoing large, phase III efficacy trials," reads a joint press release issued in this regard.
"The development of an effective and tetravalent dengue vaccine is a very high priority for the large population of Bangladesh, which is now having increasingly severe dengue outbreaks," said Rashidul Haque, senior scientist and lead investigator (icddr,b).
"We are proud to participate in the evaluation of the TV005 vaccine in the Bangladeshi population and hope that our work will accelerate the development of dengue vaccines for our country."
Dr Beth Kirkpatrick, leading the UVM team, emphasised the significance of TV005 being a single-dose tetravalent dengue vaccine, a unique feature in the realm of dengue vaccines.
He said, "The TV005 vaccine is the only single-dose tetravalent dengue vaccine, which is an important feature of this vaccine. It also appears to prompt immune responses to all four of the dengue serotypes, which is important for any tetravalent dengue vaccine."
Both Dr Kirkpatrick and Dr Rashidul Haque expressed hope that their work would contribute to the development of dengue vaccines for Bangladesh and the wider South Asian population.
All tetravalent dengue vaccines aspire to have a balanced immune response to all four serotypes.
Pharmaceutical companies Sanofi and Takeda have had success with other tetravalent dengue vaccines, completing their own phase III trials. The 3-dose Sanofi vaccine is limited to children under nine years of age with known past exposure to dengue. The 2-dose Takeda vaccine has had the best response to dengue serotype 2.
Ongoing studies, including those by the DIDI team, will continue to explore the efficacy, durability, and immune responses of this groundbreaking vaccine.