Immune cell interaction prompts new dengue vaccine

dengue hand-main
A worker puts her hand in a cage with male genetically modified Aedes aegypti mosquitoes to prove they do not bite Copyright: Panos/Andrew Testa

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  • A type of skin cell attracts the immune cell gamma delta T to the infection site
  • Interaction of two immune cells creates a synapse that kills infected cells
  • Synapses promise more inclusive and efficient vaccines against viruses

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[MANILA] A newly discovered physical interaction between two types of immune cells may lead to the development of a new vaccine against mosquito-borne viruses, particularly dengue, according to a study.

Among the several mosquito-borne viral diseases, dengue is considered the most significant for morbidity and mortality. WHO estimates that 50—100 million new dengue-virus infections occur annually, with about 200,000—500,000 of them life-threatening.

Researchers at Duke-National University of Singapore’s medical school found that a mast cell — a type of immune cell that is very abundant in the skin and serves as the body’s first line of defence against infections — attracts another type of immune cell, the gamma delta T cell, to the infection site.

“It helps to understand the type of immune response that is protective so that we can plan for vaccines that are specifically able to induce protection.”

Ashley St. John, Duke-National University of Singapore

In the study, published in The Journal of Clinical Investigation and shared to the media last week, the researchers observed that the T cell physically interacted with the mast cell through a receptor in the latter called the endothelial protein C receptor. This interaction — an ‘immune synapse’— led the T cell to activate, proliferate, and produce interferon gamma, causing the immune cells to kill cells that are infected with the dengue virus.

“These [immune synapse] structures of cells in the process of communication were very exciting and visually striking to us when we first made this observation,” says Ashley St. John, assistant professor at of Duke-NUS and co-author of the study, along with Chinmay Mantri, a research fellow.  “[Our discovery provided] a glimpse into the ways that cells must work together to fight infection.”

dengue infographic

Learning about the process immune cells go through when a virus first enters the body is important. “The earliest moments of infection are probably critical for the host to identify the virus and begin to mount a strategy for protection; but hardly anything was known about how the virus is initially detected,” says St. John. “In this study, we showed that the interactions between immune cells in the skin are very important for clearing an infection. It will be key to determine if similar responses occur following vaccination; and if they do, whether this also promotes immunity.”

In Singapore, 3,285 dengue cases were reported in 2018 alone; this figure is 20 per cent more than the reported cases in 2017. This month (February), two elderly men have died from dengue, the first two dengue-related deaths reported in Singapore in 2019. Elsewhere in the Asia-Pacific region, dengue cases have seen a rise in 2018.
“We think that understanding the earliest events that promote protection against the virus is important for developing or refining existing vaccines,” says St. John. “It helps to understand the type of immune response that is protective so that we can plan for vaccines that are specifically able to induce protection.”

Anna Ong-Lim, president of the Pediatric Infectious Disease Society of the Philippines, says any effective vaccine is welcome, given that mosquito-borne viruses, particularly dengue, pose a big burden globally, not just in the Asia-Pacific region. “Trying to elicit a cytotoxic response [in developing vaccines] is a different approach which could work,” says Ong-Lim. However, “the inflammatory response is what leads to the symptoms [of dengue, particularly]. This might not be reversed even if there was cell-killing activity”.

If the vaccines St. John and her team are planning to develop are accepted in the market, accessibility would be another obstacle, says Ong-Lim. “Cost effectiveness analyses would have to be made to justify the expense [of administering the vaccines],” she said.
This piece was produced by SciDev.Net’s Asia & Pacific desk.