Child protected by a fading vaccine shield against dengue mosquitoes

Dengue Vaccine Dilemma: Benefits vs. Risks - What Parents Need to Know

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Soraya Malik in Health & Wellness September 2025 • 4 min read.

"A closer look at the Dengvaxia vaccine and the complexities of dengue immunity, to help you make informed decisions."


Dengue fever is a significant health concern, especially in tropical and subtropical regions. The development of the Dengvaxia vaccine (CYD-TDV) was initially hailed as a breakthrough in combating this widespread disease. However, recent studies, including a post-hoc analysis by Sridhar et al., have revealed a complex picture regarding its safety and efficacy.

The analysis indicated an increased risk of severe dengue virus (DENV) disease among individuals who were seronegative for dengue (meaning they had not previously been exposed to the virus) before vaccination. This unexpected finding has raised concerns about the potential for the vaccine to do more harm than good in certain populations.

This article dives into the key findings and competing explanations surrounding the Dengvaxia vaccine. By understanding the nuances of dengue immunity and the potential risks associated with the vaccine, parents and healthcare providers can make more informed decisions.

The Serostatus Paradox: Why Prior Exposure Matters

Child protected by a fading vaccine shield against dengue mosquitoes

The central issue with the Dengvaxia vaccine lies in its interaction with an individual's pre-existing immunity to dengue. Dengue is caused by four distinct serotypes of the dengue virus (DENV 1-4). Infection with one serotype provides lifelong immunity to that specific serotype, but only short-term protection against the others. Subsequent infections with different serotypes can lead to more severe disease.

Sridhar et al.'s analysis highlighted that children who were seronegative for dengue prior to vaccination experienced higher rates of virologically confirmed dengue (VCD) and an increased risk of severe VCD after vaccination. This observation aligns with the concept of antibody-dependent enhancement (ADE).

  • Antibody-Dependent Enhancement (ADE): In ADE, non-neutralizing antibodies (those that don't completely block the virus) bind to the virus and facilitate its entry into immune cells, leading to increased viral replication and a more severe immune response.
  • T-Cell-Mediated Immunopathology: Slifka and Amanna propose an alternative explanation, focusing on T-cell responses. They suggest that if protective antibody levels decline after vaccination, but DENV-specific T-cell memory remains, a subsequent infection could trigger an overly robust T-cell response, leading to increased immunopathology.
Additional complexity arises from the observation that vaccine efficacy diminishes within 3 to 4 years post-immunization. This further reinforces the need for careful consideration of individual serostatus and immune history when evaluating vaccine suitability.

Navigating the Dengue Vaccine Landscape

The findings surrounding the Dengvaxia vaccine underscore the complexities of vaccine development and the importance of understanding individual immune responses. While the vaccine offers protection to individuals with prior dengue exposure, it can pose risks to those who have never been infected.

For parents and healthcare providers in dengue-prone areas, careful assessment of dengue serostatus is crucial before making vaccination decisions. Alternative strategies, such as vector control and early diagnosis and treatment of dengue infections, remain essential components of a comprehensive dengue prevention program.

Ongoing research continues to refine our understanding of dengue immunity and to develop safer and more effective vaccines. The insights gained from the Dengvaxia experience will undoubtedly inform future efforts to combat this global health challenge.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

How does Dengvaxia work, and why is it potentially risky for some people?

Dengvaxia works by stimulating the body's immune system to produce antibodies against the four serotypes of the dengue virus (DENV 1-4). However, it has been observed that individuals who had not been previously exposed to dengue (seronegative) before vaccination are at increased risk of severe dengue if they get infected after being vaccinated. This is because the vaccine may not provide sufficient protection in these individuals and could potentially worsen the disease upon natural infection.

2

What is antibody-dependent enhancement (ADE), and how does it relate to concerns about the Dengvaxia vaccine?

Antibody-dependent enhancement (ADE) is a phenomenon where non-neutralizing antibodies bind to the dengue virus, facilitating its entry into immune cells. This process leads to increased viral replication and a more severe immune response, potentially worsening the infection. Sridhar et al.'s analysis suggests ADE may play a role in the increased risk of severe dengue in Dengvaxia recipients who were seronegative at the time of vaccination.

3

Besides ADE, what other immunological mechanism, like T-cell-mediated immunopathology, could explain the risks associated with Dengvaxia?

T-cell-mediated immunopathology is an alternative explanation that focuses on the role of T-cells in dengue infection. Slifka and Amanna propose that if protective antibody levels decline after Dengvaxia vaccination but DENV-specific T-cell memory remains, a subsequent infection could trigger an overly robust T-cell response. This heightened response could lead to increased immunopathology and more severe symptoms.

4

What specific findings from Sridhar et al.'s analysis raised concerns about the use of Dengvaxia in individuals without prior dengue exposure?

Sridhar et al.'s analysis revealed that children who were seronegative for dengue prior to receiving the Dengvaxia vaccine experienced higher rates of virologically confirmed dengue (VCD) and an increased risk of severe VCD after vaccination. This finding suggests that the vaccine may not be suitable for individuals without prior dengue exposure and could potentially increase their risk of severe disease.

5

How long does the protection from the Dengvaxia vaccine last, and what are the implications of its diminishing efficacy?

The efficacy of the Dengvaxia vaccine diminishes within 3 to 4 years post-immunization. This means that the protective effects of the vaccine wane over time, potentially leaving individuals vulnerable to dengue infection after a few years. This highlights the importance of understanding the long-term effects of the vaccine and considering booster doses or alternative prevention strategies to maintain protection against dengue.

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