The components of the immune response that protect humans from dengue virus (DENV) infections remain largely unsolved, posing challenges for researchers seeking to enhance vaccine development. A recent study has shed light on how to strengthen immunity against DENV. Scientists from the US and Philippines discovered that specific antibodies, termed envelope dimer epitope (EDE)-like antibodies, are crucial for establishing broad immunity against various DENV serotypes following either natural infection or vaccination. This research, published in Science Translational Medicine, represents a significant advancement in understanding dengue immunity and could pave the way for more effective treatments.
Dengue fever, a major global health concern caused by four distinct DENV serotypes, is the most prevalent vector-borne viral disease, placing nearly half of the world’s population at risk, particularly in Southeast Asia, Africa, and the Americas. A 2013 study revealed that the economic burden of dengue in Southeast Asia surpasses that of diseases such as Japanese encephalitis and hepatitis B. However, creating a universally effective vaccine has been complex due to intricate immune mechanisms. In fact, the initial immune response to a person’s first DENV infection can ironically increase the risk of severe illness during subsequent infections with different DENV serotypes-a phenomenon known as antibody-dependent enhancement. This occurs when non-neutralizing antibodies bind to immature virus particles, allowing them to enter immune cells and exacerbate the infection. All severe cases requiring hospitalization arise from such second infections.
As vaccines aim to simulate natural infections, the risk of antibody-dependent enhancement complicates dengue vaccine strategies, leading to recommendations only for those with prior exposure to the virus. Genuine protection, known as “secondary immunity,” develops after exposure to at least two different DENV serotypes. Two primary vaccines-Dengvaxia and QDENGA-are currently licensed in some regions and are most effective for those previously infected with dengue, necessitating laboratory confirmation of previous infections for Dengvaxia.
In June 2017, a significant dengue outbreak occurred in Cebu, Philippines, following the administration of the vaccine to children aged 9-14. The researchers tracked a cohort of 2,996 children, with 1,782 receiving the vaccine. Blood samples were collected before vaccination and again 17 to 28 months later, coinciding with the outbreak, predominantly caused by DENV2. The team analyzed various antibody types, including EDE-like antibodies, neutralizing antibodies, and binding antibodies.
Findings underscored the pivotal role of EDE-like antibodies, noted for their high prevalence in children with secondary immunity-between 81.8% and 90.1% had detectable levels. In contrast, EDE-like antibodies were rarely found in those who had only primary immunity (4%-12%). This suggests that EDE-like antibodies are instrumental in establishing immunity against dengue. The quantity of EDE-like antibodies was strongly correlated with neutralization across all four DENV serotypes, indicating their importance for broad protection.
The study revealed that both natural DENV infections during the outbreak and vaccination significantly increased EDE-like antibodies, along with binding and neutralizing antibodies, even among children with existing secondary immunity. Higher EDE-like antibody levels were consistently linked to a reduced likelihood of symptomatic dengue and hospitalization, showcasing their protective effects across multiple serotypes. However, these antibodies displayed limited capacity to prevent viral replication, making them less effective against new infections but more protective against severe disease.
Perhaps the most crucial observation was that EDE-like antibodies statistically accounted for a significant portion of the protective effects of other antibodies. When incorporated into statistical models, the impact of other antibodies diminished, suggesting EDE-like antibodies are a primary determinant of broad immunity against dengue.
Despite certain limitations, such as a limited number of dengue cases assessed for protection against all serotypes, this study marks a notable advancement in dengue research. The findings help elucidate the immune responses necessary for protection, with EDE-like antibodies demonstrating how other antibody types contribute to defense. Further studies will be essential to formally validate EDE-like antibodies as reliable indicators of vaccine efficacy. Successfully validating these antibodies could lead to the design of vaccines that elicit higher levels of EDE-like antibodies, ultimately enhancing protection against dengue.
Original Source: https://www.thehindu.com/sci-tech/science/landmark-study-offers-new-insights-into-what-protects-against-dengue/article69918933.ece
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Publish Date: 2025-08-12 05:30:00
