Using mice to combat dengue

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KUCHING: Researchers from Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have found a practical way to induce a strong and broad immunity to the dengue virus based on proof-of-concept studies in mice.

The study is reported in a paper titled ‘Sequential immunisation induces strong and broad immunity against all four dengue virus serotypes’ published in NPJ Vaccines, said SMART in a media statement yesterday.

Dengue is a mosquito-borne viral disease with an estimated 100 million symptomatic infections every year and is an endemic in over 100 countries.

The dengue virus (DENV) consists of four antigenically distinct serotypes and there is no lasting immunity following infection with any of the DENV serotypes, meaning someone can be infected again by any of the remaining three variants of DENVs.

Today, Dengvaxia is the only vaccine available to combat dengue. It consists of four variant dengue antigens, one for each of the four serotypes of dengue, expressed from attenuated yellow-fever virus.

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The current three doses of immunisation with the tetravalent vaccine induce only suboptimal protection against DENV1 and DENV2.

Furthermore, in people who have not been infected by dengue, the vaccine induces a more severe dengue infection in the future. Therefore in most parts of the world, the vaccination is only given to those who have been previously infected.

To help overcome these issues, SMART researchers tested on mice whether sequential immunisation (or one serotype per dose) induces stronger and broader immunity and found that it induced significantly higher levels of virus-specific T cell responses than tetravalent immunisation.

Moreover, sequential immunisation induced higher levels of neutralising antibodies to all four DENV serotypes.

“The principle of sequential immunisation generally aligns with the reality for individuals living in dengue endemic areas, whose immune responses may become protective after multiple heterotypic exposures,” said SMART AMR principal investigator and senior author of the study Professor Eng Eong Ooi.  

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“We were able to find a similar affect based on the use of sequential immunisation, which will pave the way for a safe and effective use of the vaccine and to combat the virus.”

Upon these promising results, he said the investigators would aim to test the sequential immunisation in humans in the near future.

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