Dengvaxia Dengue Vaccine Description
Sanofi Pasteur's Dengvaxia (CYD-TDV) is a live attenuated tetravalent chimeric vaccine made using recombinant DNA technology by replacing the PrM (pre-membrane) and E (envelope) structural genes of yellow fever attenuated 17D strain vaccine with those from the four dengue serotypes.
Dengvaxia is indicated for the prevention of dengue disease which is caused by dengue virus serotypes 1, 2, 3, and 4. Dengvaxia is not approved for use in individuals not previously infected by any of the dengue virus 4 serotypes or for whom their immunization information is unknown.
In 2015, Sanofi Pasteur introduced the first dengue vaccine which is registered in several of the most endemic countries in the world.
Sanofi announced in 2017 that people who receive the vaccine and have not been previously infected with a dengue virus may be at risk of developing severe dengue if they get dengue after being vaccinated.
On May 1, 2019, Dengvaxia (Dengue Tetravalent Vaccine, Live) was approved by the U.S. FDA for use in children 9-16 years old living in an area where dengue is common (the US territories of American Samoa, Puerto Rico, and the US Virgin Islands), with laboratory-confirmed prior dengue virus infection.
Each year, 390 million people are infected, of which 96 million people show clinical symptoms. An estimated 500,000 people with severe dengue require hospitalization each year, and about 2.5% of those affected die from dengue. The American region alone reported 3.1 million cases, with more than 25,000 classified as severe in 2019, says the World Health Organization.
Sanofi Pasteur Inc. is the manufacturer of the Dengvaxia vaccine.
Dengvaxia Dengue Vaccine Indication
Dengvaxia is indicated for use in individuals 9 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas.
Dengvaxia is approved for use in several endemic countries in Latin America and Asia, where reducing the human and economic burden of dengue is critical. Approximately 5% of patients with dengue virus disease progress to develop a severe, life-threatening disease called Severe Dengue.
According to the U.S. CDC, early dengue clinical findings are nonspecific, but require a high index of suspicion, because recognizing early signs of shock and promptly initiating intensive supportive therapy can reduce the risk of death among patients with severe dengue to <0.5%.
The sequence variability between the four serotypes is up to 40% and between strains within a serotype is ~3%.
When an individual is infected with one dengue serotype, subsequent infection with another serotype may result in the development of more intense infections.
As an example, researchers from Duke-NUS Medical School reported that the dengue virus serotype 2 (DENV2) changes its shape through mutations in Envelope protein to evade vaccines and therapeutics.
The Pan American Health Organization (PAHO) published a report on June 10, 2020, which found 97.3% of these arboviral cases were dengue. The new PAHO data indicates there are 4 dengue serotypes are circulating in Brazil, Colombia, and Mexico. While in Guatemala, Guadeloupe, French Guiana, Saint Martin, Argentina, and Paraguay report the circulating of 3 dengue serotype combinations.
Dengvaxia Dengue Vaccine Dosage
Dengvaxia (CYD-TDV) currently given as a 3-dose series 6 months apart (at months 0, 6, and 12). It is administered as a subcutaneous Injection.
Dengvaxia Dengue Vaccine Side Effects
The most commonly reported side effects by those who received Dengvaxia were a headache, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever.
Dengvaxia Dengue Vaccine Limitation of Use
Dengvaxia is not for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown. The CDC says before being vaccinated with Dengvaxia, inform your healthcare provider if you have dengue symptoms or live in, or have recently traveled to an area with a risk of dengue.
Those not previously infected are at increased risk for Severe Dengue disease when vaccinated and subsequently infected with the dengue virus.
This antibody-dependent enhancement phenomenon is proposed to be due to antibodies elicited in a primary infection against the first serotype subsequently binding to but not neutralizing the other serotype in the second infection. Blood testing detects the dengue virus or antibodies produced in response to dengue infection.
Previous dengue infection can be assessed through a medical record of a previous laboratory-confirmed dengue infection or through serological testing prior to vaccination.
Dengue Diagnostic Tests
There is no FDA cleared test available to determine a previous dengue infection. Available non-FDA cleared tests may yield false-positive results (e.g., due to cross-reactivity with other flaviviruses). There are several different types of blood tests that can indicate a dengue infection:
- Molecular tests for dengue virus (PCR)—detect the presence of the virus itself; these tests can diagnose dengue fever up to 7 days after the onset of symptoms and can be used to determine which of the 4 different serotypes of dengue virus is causing the infection.
- Antibody tests, IgM and IgG—detect antibodies produced by the immune system when a person has been exposed to the virus; these tests are most effective when performed at least 4 days after exposure.
- Complete blood count (CBC)—to look for low platelet count typical of the later stages of the illness and to detect the decrease in hemoglobin, hematocrit, and red blood cell (RBC) count (evidence of anemia) that would occur with blood loss associated with severe dengue fever.
- Basic metabolic panel (BMP) – to monitor kidney function and look for evidence of dehydration.
Dengvaxia Dengue Vaccine News
November 17, 2020 - Study published by The Lancet: A 2-dose CYD-TDV regimen might be an alternative to the licensed 3-dose regimen in individuals who are dengue seropositive at baseline and aged 9 years and older. Vaccination with a reduced number of doses could lead to improved vaccine compliance and coverage, especially in low-resource settings.
October 16, 2020 - The Philippines Supreme Court has approved the petition to transfer all Dengvaxia-related cases to a single Regional Trial Court.
October 14, 2020 - The U.S. CDC reissued a Travel Alert for the Americas regarding various Dengue outbreaks.
July 2, 2020 - The U.S. CDC reported US States have confirmed 124 dengue cases and the US Territories have reported 218 dengue cases during 2020.
June 23, 2020 - More than 1.6 million cases of dengue have been reported in the Americas in the first five months of 2020, drawing attention to the need to continue eliminating mosquito vectors of disease even in the midst of the COVID-19 pandemic.
June 9, 2020 - To notify visitors of their health risks when visiting the Americas, the US CDC reissued a Level 1 Travel Alert. Dengue is an ongoing risk in many parts of Central and South America, Mexico, and the Caribbean (map). Travelers to areas of risk should protect themselves by preventing mosquito bites.
May 21, 2020 - The CDC issued a Travel Alert which says 'Dengue is a risk in many parts of Central and South America, Mexico, and the Caribbean.'
January 22, 2020 - The US FDA 'approved your request submitted and received on July 23, 2019, to supplement your Biologics License Application (BLA) under section 351(a) of the Public Health Service Act for Dengue Tetravalent Vaccine, Live (DENGVAXIA) to revise the NDC number for the Saline Diluent and update the package insert and diluent container labeling to include the new NDC number.'
December 27, 2019 - A study reported on December 27, 2019, the ‘screen and vaccinate’ strategy is more effective in reducing the number of hospitalized and severe dengue cases. The World Health Organization (WHO) recommended the option of a dengue screen and vaccinate policy is likely to have a positive impact both at the individual and population level, across a wide range of transmission settings. And, the WHO screen and vaccinate intervention model was found cost-effective in all countries considered, except for very low transmission settings. The overall population impact of a screen and vaccinate approach is also likely to be improved by the use of several rounds of screening (up to 48% reduction in dengue hospitalization over 10 years with 5 rounds).
May 1, 2019 - Division of Vaccines and Related Product Applications (DVRPA) Office of Vaccines Research and Review.
March 7, 2019 - The U.S. FDA approved the use of Dengvaxia for children ages 9-16 and is considered a significant medical advance in the prevention of dengue, which is considered an unmet medical need by the FDA. The European Commission has granted marketing authorization for Dengvaxia, Sanofi’s dengue vaccine. The marketing authorization follows the October 18, 2018, recommendation by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) to approve the use of the dengue vaccine in European endemic areas. Dengvaxia will be available in Europe to prevent dengue disease in individuals 9-45 years of age with a documented prior dengue infection and who are living in endemic areas.
December 19, 2018 - The European Commission has granted marketing authorization for Dengvaxia®, Sanofi's dengue vaccine. The marketing authorization follows the October 18, 2018, recommendation by the European Medicines Agency's Committee for Medicinal Products for Human Use to approve the use of the dengue vaccine in European endemic areas.
September 7, 2018 - The WHO issued a position paper regarding dengue vaccines.
February 1, 2018 - Editorial published by The Lancet: The dengue vaccine dilemma.
October 4, 2016 - Sanofi Pasteur announced that Dengvaxia had received market approval in Mexico, the Philippines, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand, and Singapore.
December 23, 2015 - The Philippines became the first Asian country to approve the commercial sale of Dengvaxia. In April 2016, the Department of Health launched the dengue vaccination campaign in regions Central Luzon, Calabarzon, and Metro Manila, where about 700,000 individuals received at least one dose of the vaccine.
September 14, 2014 - The Lancet: the past decade has also seen an upsurge in research on dengue virology, pathogenesis, and immunology and in the development of antivirals, vaccines, and new vector-control strategies that can positively impact dengue control and prevention.