Taiwanese Institutes Develop Bispecific Antibody to Combat Dengue Inflammation

Taiwanese researchers have made a significant breakthrough in the fight against dengue fever, a persistent public health challenge. Scientists from the National Health Research Institutes (NHRI) and the medical college of National Cheng Kung University (NCKU) have collaborated to develop a novel bispecific antibody. This antibody aims to block the inflammatory mechanisms triggered by the dengue virus, offering a potential new treatment strategy.

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Dengue fever has always been an important public health issue. Every year, hundreds of millions of people worldwide are infected by the bites of Aedes aegypti and Aedes albopictus mosquitoes, causing tens of millions of deaths, but there are still no effective vaccines or treatments available.

Dengue fever, transmitted by Aedes mosquitoes, affects hundreds of millions globally each year, causing millions of deaths. Current treatments primarily focus on supportive care, with no effective vaccines or specific antiviral drugs available. The new research, published in the *Journal of Biomedical Science*, identifies that dengue virus infection in macrophages leads to a "cytokine storm." This overreaction of the immune system causes systemic inflammation, shock, and multi-organ dysfunction, characteristic of severe dengue.

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After macrophages are infected by the dengue virus, they produce a large amount of cytokines, causing an over-immune response, producing a 'cytokine storm,' which can lead to systemic inflammation, shock, and multi-organ dysfunction.

The research team confirmed that the dengue virus activates this severe inflammatory response through two key innate immune receptors: CLEC5A and TLR2. By developing a bispecific antibody that simultaneously blocks both receptors, they aim to disrupt the virus's inflammatory pathway. Professor Wang Chen-jen from NCKU's medical college highlighted that this antibody has shown efficacy against all four dengue virus serotypes, including strains with mutations associated with severe disease. This suggests a broad potential to inhibit dengue virus-induced inflammation across different strains and serotypes.

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After confirming the roles of CLEC5A and TLR2, the team began to try to block both receptors simultaneously and spent several years producing a 'bispecific antibody' as a new therapeutic strategy.

The researchers are currently seeking patents for the bispecific antibody and plan to conduct further animal model and preclinical studies to assess its safety and therapeutic effectiveness. They are also open to industry collaborations and technology transfers, with the goal of advancing the antibody into clinical trials as soon as possible. This development offers a promising new avenue for treating severe dengue and potentially other flaviviruses, including COVID-19.

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The bispecific antibody has good effects on dengue viruses of four different serotypes, carrying severe disease-related mutations, indicating that this antibody has the potential to inhibit the inflammatory response of dengue viruses across serotypes and virus strains.