Dengue Vaccine (Dengvaxia) Recommendations
Dengvaxia should only be administered to children and adolescents aged 9-16 years who have laboratory-confirmed previous dengue infection and are living in dengue-endemic areas of the United States and its territories. 1, 2
Strict Eligibility Requirements
Age and Geographic Restrictions
- Vaccinate only children aged 9-16 years residing in endemic U.S. areas including Puerto Rico, American Samoa, U.S. Virgin Islands, Federated States of Micronesia, Republic of Marshall Islands, and Republic of Palau 2
- Do not vaccinate travelers or visitors to endemic areas—only permanent residents qualify 1
Mandatory Pre-Vaccination Testing
- Laboratory confirmation of previous dengue infection is absolutely required before administering any dose 1, 2
- Use a highly specific serodiagnostic test detecting anti-DENV immunoglobulin G 2
- Never vaccinate dengue-seronegative individuals due to the severe risk of antibody-dependent enhancement (ADE) leading to severe dengue upon subsequent natural infection 1, 3
Critical Safety Concern
The most important caveat is that Dengvaxia increases the risk of severe dengue in seronegative children who experience their first natural dengue infection after vaccination 2. This is why the CDC explicitly contraindicated the vaccine in individuals without laboratory-confirmed previous dengue infection 1. The mechanism involves antibody-dependent enhancement, where vaccine-induced antibodies paradoxically facilitate viral entry into cells during primary natural infection, leading to worse outcomes 3.
Vaccination Schedule and Administration
- Administer three doses at 0,6, and 12 months 4, 5
- The vaccine is a live-attenuated, chimeric tetravalent formulation built on a yellow fever 17D backbone 2
- Can be given simultaneously with other vaccines if indicated 2
Timing After Natural Infection
When vaccinating after a documented acute dengue infection, consider the kinetics of immune responses—both the nature and timing of vaccination relative to infection can impact vaccine take and clinical benefit 5. While specific timing intervals are not firmly established in guidelines, ensure adequate documentation of previous infection before proceeding 5.
Efficacy Data
In phase 3 trials involving over 30,000 children and adolescents in Latin America and Asia, Dengvaxia demonstrated:
- 60.8% and 56.5% protective efficacy against virologically-confirmed dengue in the respective trials 4
- Significant protection against severe dengue, dengue hemorrhagic fever, and dengue-related hospitalization in children aged 9 years and older 4
- Efficacy maintained through 25 months of active surveillance 4
Who Should NOT Receive Dengvaxia
- Children without documented previous dengue infection (absolute contraindication) 1
- Children under 9 years or over 16 years of age 1, 2
- Travelers or temporary visitors to endemic areas 1
- Individuals living in non-endemic regions 1
Alternative Vaccine Considerations
A second dengue vaccine (Qdenga/Takeda) has been approved by WHO but shows imbalanced immune responses against DENV-3 and DENV-4 serotypes in seronegative individuals, raising similar ADE concerns 3. This vaccine is recommended only in highly endemic countries 3.
Public Health Context
The WHO Strategic Advisory Group of Experts (SAGE) recommended that countries with high dengue endemicity consider introducing Dengvaxia as part of an integrated disease prevention strategy 4. The ACIP recommendation in 2021 marked a milestone as the first dengue vaccine approved for use in the United States, and notably, one of the first vaccines requiring mandatory pre-vaccination laboratory testing 2, 6.