In a new study, scientists have discovered more about how the body protects against dengue fever, one of the world’s most common mosquito-borne illnesses, prompting hopes for more effective vaccines against the disease.

Dengue fever is a viral infection transmitted through the bites of mosquitoes infected by any of four closely related dengue viruses (DENV-1, DENV-2, DENV-3 and DENV-4). According to the World Health Organization, approximately half of the world’s population is at risk of dengue, especially in tropical and sub-tropical climates. There are around 100 to 400 million infections every year, and while many are asymptomatic, the virus can sometimes cause more serious problems, and even death.

Although some vaccines offer a degree of protection, especially for people who have not previously been exposed to the virus, creating a universally effective vaccine has been difficult. One of the main reasons for this is our limited understanding of the complex immune responses involved. For example, it’s unclear why the immunity a person gets after their first infection increases the risk of severe disease if a different type of dengue virus subsequently infects them.

However, new research by scientists from the US and the Philippines, published in Science Translational Medicine, has revealed fresh insights into how the body fights the virus.

The researchers followed a group of nearly 3,000 children aged 9 to 14 in the Philippines for two years to see what happened to their immune systems after a mass Dengvaxia vaccination campaign. They took blood samples from vaccinated and unvaccinated children before and after the campaign and compared those who ended up getting dengue with those who stayed healthy. This allowed them to see what was different about the immune responses in the two groups.

New antibody targets for vaccines

The study found that specific quaternary antibodies known as EDE-like antibodies (envelope dimer epitope) are much more common in children who have had dengue fever two or more times but are rare after a single infection. These antibodies were linked to a lower risk of symptomatic dengue and more severe dengue, which could make them useful targets for future vaccines.

“Antibodies targeting quaternary epitopes help explain the broad cross-protection observed in those with multiple prior DENV exposures, making them useful for evaluation and development of future vaccines and therapeutics,” wrote the researchers.

The research may also lead to better tools to assess a person’s immunity and risk of becoming ill in places where dengue is endemic.

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