|Target disease||Dengue fever|
The development of vaccine for dengue fever began as early as 1929, but has been hindered first by incomplete knowledge of the disease pathogenesis, and later by the need to simultaneously create a stable immunity against all four dengue serotypes. Several vaccine candidates are in development including live attenuated, inactivated, DNA and subunit vaccines. Live attenuated vaccine candidates are the furthest along in development.
In 2016 a partially effective vaccine for dengue fever (Dengvaxia) became commercially available in the Philippines and Indonesia. It has also been approved for use by Mexico, Brazil, El Salvador, Costa Rica, and Paraguay. In Indonesia it costs about US$207 for the recommended three doses.
CYD-TDV, sold under the brand name Dengvaxia, is a live attenuated tetravalent chimeric vaccine made using recombinant DNA technology by replacing the PrM (pre-membrane) and E (envelope) structural genes of the yellow fever attenuated 17D strain vaccine with those from four of the five dengue serotypes. Ongoing phase III trials in Latin America and Asia involve over 31,000 children between the ages of 2 and 14 years. In the first reports from the trials, vaccine efficacy was 56.5% in the Asian study and 64.7% in the Latin American study in patients who received at least one injection of the vaccine. Efficacy varied by serotype. In both trials vaccine reduced by about 80% the number of severe dengue cases. 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 9 years of age, but considerably greater (81.9%) for children who were seropositive (indicating previous dengue infection) at baseline. The vaccination series consists of three injections at 0, 6 and 12 months. The vaccine was approved in Mexico, Philippines, and Brazil in December 2015, expected to be the first among the 20 countries in the coming weeks. Tradenamed Dengvaxia, it is approved for use for those aged nine and older and can prevent all four serotypes.
DENVax is a recombinant chimeric vaccine with DENV1, DENV3, and DENV4 components on a dengue virus type 2 (DENV2) backbone developed at Mahidol University in Bangkok. Phase I and II trials are ongoing in the United States, Colombia, Puerto Rico, Singapore and Thailand.
TetraVax-DV is a tetravalent admixture of monovalent vaccines that were tested separately for safety and immunogenicity. The vaccine passed phase I trials and is being tested in phase II studies in Thailand and Brazil. In Brazil, the studies are being done in collaboration with the Instituto Butantan.
TDEN PIV is inactivated tetravalent vaccine undergoing phase I trials as part of a collaboration between GSK and the Walter Reed Army Institute of Research. A synergistic formulation with another live attenuated candidate vaccine (prime-boost strategy) is also being evaluated in a phase II study. In prime-boosting, one type of vaccine is followed by a boost with another type in an attempt to improve immunogenicity.
Manufacturer in India and Vietnam
Panacea Biotec and Biological E. Limited have vaccine candidates in the earliest stages of development. A company in Vietnam (VABIOTECH) is conducting safety tests and developing a clinical trial plan. All three companies are involved in studies of a TetraVax-DV vaccine in conjunction with the National Institutes of Health.
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