Dengue vaccine is a vaccine used to prevent dengue fever in humans. Development of dengue vaccines began in the 1920s, but was hindered by the need to create immunity against all four dengue serotypes. As of 2023, there are two commercially available vaccines, sold under the brand names Dengvaxia and Qdenga.
Dengvaxia is only recommended in those who have previously had dengue fever or populations in which most people have been previously infected. The value of Dengavaxia is limited by the fact that it may increase the risk of severe dengue in those who have not previously been infected. In 2017, more than 733,000 children and more than 50,000 adult volunteers were vaccinated with Dengvaxia regardless of serostatus, which led to a controversy. Qdenga is designated for people not previously infected.
There are other vaccine candidates in development including live attenuated, inactivated, DNA and subunit vaccines.
History
In December 2018, Dengvaxia was approved in the European Union.
In May 2019, Dengvaxia was approved in the United States as the first vaccine approved for the prevention of dengue disease caused by all dengue virus serotypes (1, 2, 3 and 4) in people ages nine through 16 who have laboratory-confirmed previous dengue infection and who live in endemic areas. Dengue is endemic in the US territories of American Samoa, Guam, Puerto Rico, and the US Virgin Islands.
The safety and effectiveness of the vaccine was 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. The vaccine was determined to be approximately 76 percent effective in preventing symptomatic, laboratory-confirmed dengue disease in individuals 9 through 16 years of age who previously had laboratory-confirmed dengue disease.
In March 2021, the European Medicines Agency the filing package for TAK-003 (Qdenga) intended for markets outside of the EU.
In August 2022, the Indonesian FDA approved Qdenga for use in individuals six years to 45 years of age and become the first authority in the world to approve Qdenga. Qdenga was approved in the European Union in December 2022.
CYD-TDV (Dengvaxia) 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. The US Food and Drug Administration (FDA) granted the application for Dengvaxia priority review designation and a tropical disease priority review voucher. The approval of Dengvaxia was granted to Sanofi Pasteur.
The vaccine has been approved in 19 countries and the European Union, but it is not approved in the US for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown.
Dengvaxia is a 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. 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 check for 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 Organization's List of Essential Medicines. In Indonesia it costs about for the recommended three doses as of 2016.