Preliminary data regarding a live-attenuated tetravalent dengue vaccine candidate developed by Takeda show that the vaccine may be able to protect against all four serotypes of the infection, according to research presented at the annual meeting of the American Society of Tropical Medicine and Hygiene.
“Dengue is the fastest spreading mosquito-borne viral disease, with approximately 3.9 billion people around the globe at risk of infection,” Derek Wallace, vice president and global dengue program head at Takeda, told Infectious Diseases in Children. “The virus can infect people of all ages and is a leading cause of serious illness among children in some countries in Latin America and Asia. Today, dengue is classified as endemic in more than 120 countries and causes an estimated 400 million infections and almost 20,000 deaths each year.”
Wallace added that currently, dengue has no cure, and the direct medical cost of treatment is $8 billion annually.
Takeda’s vaccine candidate (TAK-003) is based on serotype 2 of the virus, a serotype that provides a “backbone” for all dengue serotypes. TAK-003 was reported to activate multiple arms of the immune response against dengue. Specifically, the vaccine produced virus-specific T-cell responses in more than 90% of those who have received the vaccine. Wallace said that after one dose of the vaccine, participants who were dengue-naive had a virus-specific T-cell response like those who had been naturally infected.
Additionally, the vaccine candidate was observed to promote NS1-specific antibodies in dengue-naive participants.
Wallace said preliminary evidence was presented demonstrating the vaccine candidate’s ability to elicit type-specific neutralizing antibodies that target all four dengue serotypes in most participants.
Safety concerns about the only currently licensed vaccine — Dengvaxia (Sanofi Pasteur) — arose last year after the manufacturer announced the vaccine may cause severe disease in nonimmune patients who become infected after vaccination. Evidence has shown that hospitalization rates were higher in vaccinated children aged 2 to 5 years and in vaccinated participants of any age who were not previously infected with dengue. In April, the Strategic Advisory Group of Experts on Immunization recommended that only people in dengue-endemic regions should get vaccinated if they are confirmed to have had a prior infection.
Wallace said Takeda’s phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) — a double-blind, randomized, placebo-controlled trial to determine the efficacy, safety and immunogenicity of two doses of TAK-003 administered 3 months apart — includes children between the ages of 4 and 16 years with or without previous exposures residing in endemic areas. The study has included more than 20,000 participants, and no safety concerns have been observed in the vaccine’s completed or ongoing trials.
“We are excited to share [these] data with the scientific community to further assist in the understanding of dengue and the potential of our dengue vaccine candidate, which has been shown to activate immune responses against all four dengue serotypes,” Wallace said. “We are looking forward to receiving our first interpretable results of the pivotal phase 3 TIDES study in early 2019. We will also be publishing our primary endpoint data as quickly as possible in a peer-reviewed publication.” – by Katherine Bortz
Disclosure: Wallace is an employee of Takeda.