Dengue is one of the world’s fastest-spreading mosquito-borne diseases, with transmission increasing in many regions due to climate change. While some infected individuals develop severe illness, others clear dengue virus without ever showing symptoms. Understanding why these asymptomatic infections occur could hold important clues for immune protection and future vaccine design.

In a study published in Science Translational Medicine, led by PhD student Natnicha Jiravejchakul together with researchers Dr. Waradon Sungnak and Dr. Ponpan Matangkasombut from the Department of Microbiology, Faculty of Science, Mahidol University, in collaboration with the Wellcome Sanger Institute and international partners, a rare five-year household surveillance study in Thailand was used to identify truly asymptomatic dengue infections while the virus was still detectable in the bloodstream. Only eight asymptomatic cases were captured, underscoring how difficult these infections are to study. Together with patients experiencing mild and severe dengue, these individuals enabled a detailed comparison of immune responses across the full disease spectrum.

By analyzing more than 134,000 immune cells using single-cell technologies, the researchers uncovered clear differences between protective immunity and disease-associated immune responses. Individuals who remained asymptomatic showed distinctive activity in key immune cell types that controlled the virus without triggering excessive inflammation. In contrast, symptomatic dengue was characterized by inflammatory pathways linked to disease severity.

Overall, these findings provide new insight into the balance between antiviral immune responses and inflammation in dengue infection. Importantly, the study offers a roadmap for next-generation dengue vaccines, suggesting that future strategies may benefit from mimicking naturally protective immune responses rather than those associated with severe disease.

Read more: https://doi.org/10.1126/scitranslmed.ads5932

First-author:Waradon Sungnak, Natnicha Jiravejchakul and Tiraput Poonpanichakul

Corresponding author: Varodom Charoensawan, Sarah A. Teichmann and Ponpan Matangkasombut