Evidence indicates that CYD-TDV is partially effective in preventing infection, but may lead to a higher risk of severe disease in those who have not been previously infected and then do go on to contract the disease. It is not clear why the vaccinated seronegative population have more serious adverse outcomes. A plausible hypothesis is the phenomenon of antibody-dependent enhancement (ADE). American virologist Scott Halstead was one of the first researchers to identify the ADE phenomenon. Dr. Halstead and his colleague Dr. Phillip Russell proposed that the vaccine only be used after antibody testing, to rule out prior dengue exposure and avoid vaccination of sero-negative individuals.Common side effects include headache, pain at the site of injection, and general muscle pains. Severe side effects may include anaphylaxis. Use is not recommended in people with poor immune function. Safety of use during pregnancy is unclear. Dengvaxia is a weakened but live vaccine and works by triggering an immune response against four types of dengue virus.Dengvaxia became commercially available in 2016 in 11 countries: Mexico, the Philippines, Indonesia, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Thailand, and Singapore. In 2019 it was approved for medical use in the United States. It is on the World Health Organizations List of Essential Medicines. In Indonesia it costs about US$207 for the recommended three doses as of 2016.In 2017, the manufacturer recommended that the vaccine only be used in people who have previously had a dengue infection, as outcomes may be worsened in those who have not been previously infected.
TAK-003
TAK-003 or DENVax is a recombinant chimeric vaccine with DENV1, DENV3, and DENV4 components on a dengue virus type 2 (DENV2) backbone originally developed at Mahidol University in Bangkok and now funded by Inviragen (DENVax) and Takeda (TAK-003). Phase I and II trials were conducted in the United States, Colombia, Puerto Rico, Singapore and Thailand. Based on the 18-month data published in the journal Lancet Infectious Diseases, indicated that TAK-003 produced sustained antibody responses against all four virus strains, regardless of previous dengue exposure and dosing schedule.Data from the phase III trial, which began in September 2016, show that TAK-003 was efficacious against symptomatic dengue. TAK-003 appears to not lack efficacy in seronegative people or potentially cause them harm, unlike CYD-TDV. The data appear to show only moderate efficacy in other dengue serotypes than DENV2.In March 2021, the European Medicines Agency accepted the filing package for TAK-003 intended for markets outside of the EU. In development
TV-003/005
TV-003/005 is a tetravalent admixture of monovalent vaccines, that was developed by NIAID, that were tested separately for safety and immunogenicity. The vaccine passed Phase I trials and Phase II studies in US, Thailand, Bangladesh, India and Brazil.NIH has conducted Phase I and Phase II studies in over 1000 participants in the US.