Vaccine Info

Dengvaxia Dengue Vaccine

Description

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.

Indication

Dengvaxia is indicated for the prevention of dengue disease 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. 

The sequence variability between the four serotypes is about 25 to 40% and between strains within a serotype is ~3%. Dengvaxia is indicated in the US for use in individuals 9 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas.

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. Approximately 5% of patients with dengue virus disease progress to develop a severe, life-threatening disease called Severe Dengue.

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.

Dosage

Dengvaxia (CYD-TDV) dosage is currently given as a 3-dose series 6 months apart (at months 0, 6, and 12). It is administered as a Subcutaneous Injection.

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.

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 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.

Early 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%.

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.

A new 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).

Updates

May 1, 2019: The US Food and Drug Administration (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.

November 29, 2017Sanofi will ask health authorities to update the information provided to physicians and patients on its dengue vaccine Dengvaxia® in countries where it is approved. The request is based on a new analysis of long-term clinical trial data, which found different.

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 1, 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.

Updated
January 8th, 2020