In News:

A new study published in Science Translational Medicine has provided critical insights into dengue immunity and vaccine development. The research, conducted in the Philippines with nearly 3,000 children, highlighted the role of Envelope Dimer Epitope (EDE)-like antibodies as a key driver of broad, cross-serotype protection against dengue virus (DENV).

Dengue: Global Challenge

• Caused by four serotypes (DENV1–DENV4).
• Most common vector-borne viral disease, affecting nearly half the world’s population, particularly in Southeast Asia, Africa, and the Americas.
• Economic burden in Southeast Asia exceeds that of 17 other diseases including hepatitis B and Japanese encephalitis.
• Severe dengue typically occurs during secondary infection with a different serotype due to Antibody-Dependent Enhancement (ADE), where non-neutralising antibodies worsen infection.

Current Vaccines

• Dengvaxia – Licensed in some countries, but recommended only for those with prior dengue exposure (requires laboratory confirmation).
• QDENGA – Approved in some regions, effective mainly in pre-exposed individuals.
• Limitation: Both vaccines carry ADE risks for dengue-naïve individuals.

What are EDE-like Antibodies?

• Definition: Antibodies targeting Envelope Dimer Epitope (EDE), a quaternary structure formed by paired E proteins on the viral surface.
• Function: Broadly neutralise all four serotypes by preventing viral entry into cells.
• Key Features:
  • Broadly neutralising, cross-reactive across serotypes.
  • Common in individuals with multiple infections or vaccinated with prior exposure.
  • Rare in primary infection (detected in only 4–12% of such cases).
  • Strongly correlated with reduced disease severity and hospitalisation risk.
  • Potential biomarker for evaluating vaccine efficacy.

Study Highlights

• Conducted during a dengue outbreak in Cebu, Philippines (DENV2 dominant, followed by DENV3).
• Children with secondary immunity showed high prevalence of EDE-like antibodies (82–90%).
• These antibodies explained 42–65% of the protective effect of neutralising antibodies and 41–75% of E protein-binding antibodies, making them the primary determinant of broad protection.
• Findings:
  • Less protective against new infections but highly effective against severe disease.
  • Boosted by both natural infection and vaccination.
  • Strong predictor of reduced symptomatic dengue and hospitalisation.

Implications

• Vaccine Development: Targeting EDE could overcome ADE risks and provide universal dengue protection.
• Public Health: Potential for safer immunisation strategies in endemic regions like India.
• Therapeutics: Basis for developing monoclonal antibody treatments to deliver rapid, cross-serotype protection during outbreaks.