Dengue vaccine

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Dengue vaccine
Vaccine description
Target diseaseDengue fever
  • none

Dengue vaccine is a vaccine to prevent dengue fever in humans. The World Health Organization recommends that countries should consider vaccination with the dengue vaccine CYD-TDV only if the risk of severe dengue in seronegative individuals can be minimized either through pre-vaccination screening or recent documentation of high seroprevalence rates in the area (at least 80% by age 9 years).[1] 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.[2] This has caused a scandal in the Philippines where more than 733,000 children and more than 50,000 adult volunteers were vaccinated regardless of serostatus.[3]

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.[4]

In 2016 a partially effective vaccine for dengue fever (Dengvaxia) became commercially available in 11 countries: Mexico, the Philippines, Indonesia, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Thailand, and Singapore.[5][6][7] In Indonesia it costs about US$207 for the recommended three doses.[7] WHO updated its recommendations regarding the use of Dengvaxia in September 2018 based on the evidence that seronegative vaccine recipients have an excess risk of severe dengue compared to unvaccinated seronegative individuals. It is not clear why the vaccinated sereonegative population have more serious adverse outcomes. A plausible hypothesis is the phenomenon of antibody-dependent enhancement.[8]


CYD-TDV, sold under the brand name Dengvaxia and made by Sanofi Pasteur, 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 the four dengue serotypes.[9][10]

In 2017 the manufacturer recommended that the vaccine only be used in people who have previously had a dengue infection as otherwise there was evidence it may worsen subsequent infections.[2] The initial protocol did not require baseline blood samples prior to vaccination in order 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 Philippines government suspended the mass immunization program with the backing of the WHO which began a review of the safety data.[11]

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.[12][13] Efficacy varied by serotype. In both trials vaccine reduced by about 80% the number of severe dengue cases.[14] 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.[15] The vaccination series consists of three injections at 0, 6 and 12 months.[10] The vaccine was approved in Mexico, Philippines, and Brazil in December 2015, and in El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand and Singapore in 2016.[5] Tradenamed Dengvaxia, it is approved for use for those aged nine and older and can prevent all four serotypes.[16]

In development[edit]

DENVax or TAK-003[edit]

DENVax or TAK-003 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).[17][18] Phase I and II trials are ongoing in the United States, Colombia, Puerto Rico, Singapore and Thailand.[19] Based on the latest 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.[20]


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.[21] 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.[22]


Merck is studying recombinant subunit vaccines expressed in Drosophila cells. Studies are in phase I stage as of 2015.[22]

DNA vaccines[edit]

The Naval Medical Research Center attempted to develop a monovalent DNA plasmid vaccine, but early results showed it to be only moderately immunogenic.[19]

Manufacturer in India and Vietnam[edit]

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.[23] All three companies are involved in studies of a TetraVax-DV vaccine in conjunction with the National Institutes of Health.[24]

Society and culture[edit]

Philippines controversy[edit]

The 2017 dengue vaccine controversy in the Philippines involved a vaccination program run by the Philippines Department of Health.[6] It vaccinated schoolchildren with Sanofi Pasteur's CYD-TDV (Dengvaxia) dengue vaccine. Some of the children who received the vaccine had never been infected by the dengue virus before. 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.[2] 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.[11]


  1. ^ "Dengue vaccine: WHO position paper – September 2018" (PDF). Weekly Epidemiological Record. 93 (36): 457–476. September 7, 2018.
  2. ^ a b c "Sanofi restricts dengue vaccine but downplays antibody enhancement". CIDRAP. Retrieved 2 December 2017.
  3. ^ "DOJ orders NBI to investigate P3.5-B dengue vaccine scandal". STAT. 4 December 2017. Retrieved 14 December 2017.
  4. ^ McArthur, MA; Sztein, MB; Edelman, R (August 2013). "Dengue vaccines: recent developments, ongoing challenges and current candidates". Expert Review of Vaccines. 12 (8): 933–53. doi:10.1586/14760584.2013.815412. PMID 23984962.
  5. ^ a b "Sanofi's dengue vaccine approved in 11 countries". Reuters. 2016. Retrieved 13 August 2017.
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  7. ^ a b "Dengue Fever Vaccine Available in Indonesia". October 17, 2016.
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  9. ^ Thisyakorn, U. (2014). "Latest developments and future directions in dengue vaccines". Therapeutic Advances in Vaccines. 2 (1): 3–9. doi:10.1177/2051013613507862. PMC 3991153. PMID 24757522.
  10. ^ a b Yauch, Lauren E. (2014). "Dengue Virus Vaccine Development". Advances in Virus Research. 88: 315–372. doi:10.1016/B978-0-12-800098-4.00007-6. ISBN 9780128000984. PMID 24373316.
  11. ^ a b Steenhuysen, Julie and Hirschler, Ben. (12 December 2017). "Did Sanofi, WHO ignore warning signals on dengue vaccine?". Reuters website Retrieved 13 December 2017.
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  14. ^ "The Lancet: World's Most Advanced Dengue Vaccine Candidate Shows Promise in Phase 3 Trial". Science Newsline medicine. 10 July 2014. Retrieved 13 July 2014.
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  16. ^ Palmer, Eric (9 December 2015). "Sanofi gets first approval for long-anticipated vaccine against dengue fever". Retrieved 10 December 2015.
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