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A Simple Flow Cytometry Based Assay to Determine In Vitro Antibody Dependent Enhancement of Dengue Virus Using Zika Virus Convalescent Serum
Published on: April 10, 2018
Protective and immunological behavior of chimeric yellow fever dengue vaccine
Scott B Halstead1, Philip K Russell2
1Private Consultant, 5824 Edson Lane, North Bethesda, MD 20852, USA.
Insights
The chimeric yellow fever dengue tetravalent vaccine (CYD) showed mixed results, offering protection for some but increasing hospitalization risk for dengue virus (DENV) infection in young children and seronegative individuals.
Area of Science:
- Virology
- Immunology
- Epidemiology
Background:
- The chimeric yellow fever dengue tetravalent vaccine (CYD) was developed to provide protection against dengue virus (DENV).
- Clinical trials are essential to evaluate vaccine efficacy and safety, including potential adverse events like enhanced disease.
- Understanding immune responses and risk factors is crucial for dengue vaccine development.
Purpose of the Study:
- To analyze clinical observations from the third year of the CYD vaccine trials.
- To document both protective effects and instances of vaccination-enhanced dengue disease.
- To investigate the impact of vaccination on dengue virus (DENV) infection outcomes in different age and serostatus groups.
Main Methods:
- Clinical observations and epidemiological modeling were applied to trial data.
- Analysis focused on hospitalization rates and disease severity in vaccinated versus control groups.
- Stratification by age at vaccination and baseline dengue virus (DENV) serostatus was performed.
Main Results:
- Young children (≤5 years) vaccinated with CYD showed a 5-fold increased hospitalization rate for DENV disease compared to controls.
- Vaccination significantly reduced hospitalization for DENV infection in seropositive individuals.
- Seronegative individuals exhibited modest protection against mild/moderate disease but an increased risk of hospitalized DENV infection.
Conclusions:
- The CYD vaccine demonstrates a complex profile of protection and enhanced disease risk.
- Vaccination-enhanced dengue disease is a significant concern, particularly in seronegative populations and young children.
- Further research is needed to understand the mechanisms behind enhanced disease and to improve dengue vaccine strategies.
Abstract:
Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed.
