Nanoparticles vaccinate mice against dengue

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Using the only licensed dengue vaccine, Dengvaxia, the Philippines launched its first public immunisation program for dengue fever for more than a million children in April. But it’s recommended for children aged nine years and over. Can a safe vaccine be found in nanoparticles?
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Injections of nanoparticles immunised mice against the dengue virus for nearly seven months, a US study has shown.

Aravinda de Silva from the University of North Carolina and colleagues injected rodents with specially designed protein-studded particles and found the mice produced antibodies against one form, or serotype, of the virus for almost seven months.

The work was published in PLOS Neglected Tropical Diseases.

“Although they [nanoparticles] have been used before, this case is important because the nanoparticles have shown that they can achieve a significant antibody response to dengue for a longer time period,” says Prasad Paradkar, a research team leader at the Australian science organisation CSIRO who focuses on mosquito-borne viruses but was not involved with the study.

The mosquito-borne dengue virus currently afflicts more than 350 million people in more than 120 different countries each year.

While dengue symptoms can be as mild as a fever and achy muscles, they can also cause persistent vomiting, bleeding, difficulty breathing and even death.

But biologists have struggled to develop an effective vaccine against the disease. The main hurdle is the fact that the virus has four serotypes. If a patient has been infected by or immunised against one serotype, they often experience more severe symptoms if they later contract any of the other three serotypes.

And immunising against more than one serotype, using bits of actual dengue virus, can dial down any protection bestowed by previous immunisations.

Enter Aravinda de Silva and his lab.

They built and tested a new type of vaccine to combat serotype 2 of the dengue virus using nanoparticles studded with copies of DENV2-E, a key protein from that particular serotype.

To test their vaccine, de Silva and his team immunised 31 mice with either a control injection or one of five different formulations of their nanoparticle cocktail, which used particles of different shapes and sizes between 55 by 70 and 200 by 200 nanometres.

During the course of these immunisations and the subsequent boosters – the mice received two of these on four occasions after the initial injections – blood, bone marrow and lymph node samples were taken to measure immune response.

The results showed that the mice immunised with any of the new nanoparticle vaccines developed more antibodies and exhibited a better immune response than those that received the control injections.

The findings also showed no correlation between the size and shape of the nanoparticles on the antibody response – notable because it has been identified as a factor in other studies of nanoparticles in immunology.

Paradkar says the work is a critical step towards achieving a dengue vaccine, especially as mosquitos spread into higher latitudes.

“It [dengue fever] is a huge problem, especially in regions near the tropics. It is expected that with climate change, the mosquito population will grow and spread further geographically,” he says.

“So a lot of mosquitoes that can transmit dengue will be moving towards regions that are now considered to be temperate, either north or south of the tropics.”

But he advises people to view the report with a little scepticism as there are still important questions that remain to be answered about the process before it can be endorsed as a solution to the dengue virus.

“This is sort of the first step for developing a vaccine. They have done it only for one serotype and they have to do the experiment for the others to show that this technology is effective for all four serotypes.”

And while the researchers also need to determine if all four serotypes could be combined into a single vaccine, there may be something about using nanoparticles instead of chunks of virus that provides long-lasting, broad-spectrum protection.

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