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First steps taken in designing vaccine against global viral threats

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New research has highlighted how an immune cell receptor could be used to develop a vaccine against a dangerous family of global pathogens.

Scientists from the University of Southampton have found that a receptor on natural killer (NK) cells called KIR2DS2 is able to recognise viruses such as Hepatitis C, dengue, Zika, West Nile virus and yellow fever virus through a conserved target.

The paper is published in the journal Science Immunology.

The viruses all belong to a family of pathogens called flaviviruses, which are able to replicate in insects and animals and can infect both humans and animals. They’re recognised as a global threat to public health, infecting millions of people worldwide and causing symptoms such as internal bleeding and encephalitis (inflammation of the brain).

Normally, vaccines work by introducing a ‘dead’ form of the pathogen into a person, which allows their immune system to learn the organism’s main structures – this means that the next time that organism invades, the immune cells will recognise those structures and act quickly to kill it.

However, these viruses are able to change these protein structures, allowing them to hide from the immune response and making it particularly difficult to design a vaccine.

Now, lead researcher professor Salim Khakoo and his team of researchers have taken the first steps in creating a vaccine that could work against all flaviruses. By analysing the DNA of people infected with Hepatitis C, they were able to show that the KIR2DS2 receptor of NK cells bound to a region on the virus’ NS3 helicase protein, which didn’t show any variation in its structure. A form of white blood cell, NK cells contribute to the immune system by releasing toxic granules, which cause the invading pathogen to undergo apoptosis (a form of cell suicide).

The team were then able to show that the KIR2DS2 receptor was able to recognise this same NS3 protein in other flaviviruses, although at a different sequence.

“The NS2 helicase protein could be the key in unlocking the defence of lethal viruses that affect so many people around the world,” said professor Khakoo. “It is very exciting to discover that other viruses similar to Hepatitis C, such as Zika virus, dengue virus, yellow fever virus, Japanses encephalitis virus and in fact all flaviviruses contain a region with their NS3 helicase proteins that is recognised by exactly the same KIR2DS2 receptor.”

This is still early work, and follow up studies are needed to confirm these results. However, professor Khakoo is optimistic about the future. “We believe that by targeting this NS3 helicase region, we could make a new type of vaccine based upon natural killer cells, which can be used to help protect people from these infections.”

 

Luc Bourne

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