Dengue virus can literally make your “skin” crawl; paving way for vaccine development

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Dengue, a dreaded disease caused by a viral pathogen and transmitted by the bite of the Aedes mosquito is prevalent in tropical and subtropical countries including Singapore. An estimated 100 million symptomatic cases are reported across the globe every year with some severe cases that involve fatal haemorrhage fever and Dengue shock symptom. Currently there are no known vaccines for this disease and the only method of combating it is to prevent the breeding of the transmitting mosquitos.

A new study published in the Science Translational Medicine provides a beacon of light in this aspect. Researchers from Singapore and London have identified that the immune response elicited by the Dengue virus (DENV) results in homing of the activated immune cells in the skin, the site of entry of the pathogen. This exciting discovery opens doors for newer aspects to develop a potent dengue vaccine by targeting the skin.

The dengue virus – the first flavivirus structure to be determined – reveals an architectural structure that is different from any other virus
The dengue virus – the first flavivirus structure to be determined – reveals an architectural structure that is different from any other virus

The study has identified that specific T cells which are receptive to the infection produce antiviral components like TNF-α and interferon-γ. However, interestingly, these cells also expressed a protein called cutaneous lymphocyte associated antigen (CLA), a skin homing marker. The expression of CLA was found to be unique and specific to the response of DENV. The expression of CLA correlates with the ability of these immune cells to move to the skin during a viral infection as observed from the cells collected from patient’s skin blisters. Thus it establishes a critical surveillance mechanism used by the body to combat future dengue virus infections.

The lead author of the study Dr. Laura Rivino says, “The current vaccine formulations are composed of structural components of the virus that are ideal targets for antibodies. We observe that most of the T cell targets are derived from non-structural proteins. However, non-structural proteins are not part of the current vaccine formulations that are going through clinical trials. The implication is that these vaccines will poorly recapitulate the types of immune responses that underlie natural immunity to dengue found in recovered patients. It would be interesting and informative to look at the signatures of the T cells from individuals vaccinated with the different formulations that are currently undergoing clinical trial to understand which is able to elicit a T cell response similar to that elicited during natural infection.”

The original article can be accessed here.