Dengue vaccine
[17] The safety and effectiveness of the vaccine were determined in three randomized, placebo-controlled studies involving approximately 35,000 individuals in dengue-endemic areas, including Puerto Rico, Latin America, and the Asia Pacific region.
[17] In March 2021, the European Medicines Agency accepted the filing package for TAK-003 (Qdenga) intended for markets outside of the EU.
[8] CYD-TDV, sold under the brand name Dengvaxia and made by Sanofi Pasteur, is a live attenuated tetravalent vaccine that is administered as three separate injections, with the initial dose followed by two additional shots given six and twelve months later.
[9] Dengvaxia is a weakened but live vaccine and works by triggering an immune response against four types of dengue virus.
[17][9] Dengvaxia became commercially available in 2016 in 11 countries: Mexico, the Philippines, Indonesia, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Thailand, and Singapore.
[31] The initial protocol did not require baseline blood samples before vaccination to establish an understanding of increased risk of severe dengue in participants who had not been previously exposed.
In November 2017, Sanofi acknowledged that some participants were put at risk of severe dengue if they had no prior exposure to the infection; subsequently, the Philippine government suspended the mass immunization program with the backing of the WHO which began a review of the safety data.
[36] An analysis of both the Latin American and Asian studies at the 3rd year of follow-up showed that the efficacy of the vaccine was 65.6% in preventing hospitalization in children older than nine years of age, but considerably greater (81.9%) for seropositive children (indicating previous dengue infection) at baseline.
[21] The vaccine was approved in Mexico, the Philippines, and Brazil in December 2015, and in El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand, and Singapore in 2016.
[39][40] Phase I and II trials were conducted in the United States, Colombia, Puerto Rico, Singapore and Thailand.
[40] The 18-month data published in the journal Lancet Infectious Diseases, indicate that TAK-003 produced sustained antibody responses against all four virus strains, regardless of previous dengue exposure and dosing schedule.
[50] NIH has licensed their technology for further development and commercial scale manufacturing to Panacea Biotec,[51] Serum Institute of India,[51] Instituto Butantan,[51] Vabiotech,[51] Merck,[52] and Medigen.
[56] TDENV PIV (tetravalent dengue virus purified inactivated vaccine) is undergoing phase I trials as part of a collaboration between GlaxoSmithKline (GSK) and the Walter Reed Army Institute of Research (WRAIR).
A synergistic formulation with another live attenuated candidate vaccine (prime-boost strategy) is also being evaluated in a phase II study.
[57] In 2011, the Naval Medical Research Center attempted to develop a monovalent DNA plasmid vaccine, but early results showed it to be only moderately immunogenic.
[8][59][60] In February 2023, Qdenga was approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for people aged four years and older.
The program was stopped when Sanofi Pasteur advised the government that the vaccine could put previously uninfected people at a somewhat higher risk of a severe case of dengue fever.
[31] A political controversy erupted over whether the program was run with sufficient care and who should be held responsible for the alleged harm to the vaccinated children.
