Dengue virus vaccine candidate shows promise in mouse tests

Researchers at the University of Queensland (UQ) have developed a new vaccine candidate for dengue virus, a notoriously tricky pathogen to deal with. The new candidate has a number of advantages over existing treatments, with tests on mice using microneedle patches proving promising.

Dengue fever is one of the most prevalent diseases in tropical regions, and efforts to tackle it usually focus on prevention. Much of that involves targeting mosquitoes, the carriers of the virus, with effective new traps, genetic engineering to reduce their numbers or make the bugs resistant to the virus, or bacteria that stop the virus from growing.

There is one vaccine against dengue fever currently available, known as Dengvaxia, but it’s plagued with issues. The most serious problem is that it’s only recommended for people who have previously been infected – if administered to someone who hasn’t, it may actually make a subsequent infection more serious. Licensing restrictions also keep Dengvaxia from widespread use.

The UQ team has now developed a new vaccine candidate that may skirt those problems. The researchers created a chimera out of the dengue virus and the recently discovered Binjari virus, which infects insects and is harmless to humans. The Binjari virus forms the base, and it presents dengue virus proteins that a patient’s immune system can recognize to launch a response. This comes with a range of advantages, the team says.

“The particles exactly mimic the surface of their dengue counterpart, which induces a strong, authentic and protective immune response,” says Jovin Choo, first author of the study. “Also, it allows us to very easily manufacture high yields of the vaccine candidate in mosquito cell culture. And it only grows in insect cells, and not mammalian cells, making it extremely safe.”

The team tested out the new vaccine candidate in mice. Three doses were administered to each animal 21 days apart, with some containing an adjuvant (a substance that enhances the immune response) and some without, and some delivered subcutaneously (shallow) and others intradermal (a little deeper). Then, 10 days after the third dose they were exposed to the dengue virus.

All groups that received the vaccine with the adjuvant were completely protected against the virus. Those without the adjuvant got sick but still had much higher survival rates than the control group – 100 percent for those that received the intradermal injection, and 80 percent for subcutaneous.

A microscope image of a microneedle patch, which can deliver vaccines and other drugs painlessly

University of Queensland

But perhaps the best feature – especially for those who don’t like needles – is that the treatment could be delivered through microneedle arrays. A 1-cm2 (0.2-in2) patch contains 5,000 tiny needles coated in the vaccine, and when applied to the skin they deliver the payload painlessly and, it turns out, more effectively than a traditional hypodermic needle.

In tests on mice using microneedles to deliver the dengue vaccine, the team found that the test mice were completely protected, with 100 percent surviving following exposure compared to no survivors in the control group.

While the results are promising, it’s important to remember that mouse studies are a long way from human success. There’s plenty more work to do yet – especially because there are four strains of dengue to tackle. The researchers say that the next steps will be to expand their pre-clinical studies to these other strains, and eventually they hope to adapt the tech to other mosquito-borne viruses like the Zika, West Nile and Japanese encephalitis viruses.

The research was published in the journal npj Vaccines.

Source: University of Queensland

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