Amid growing dengue outbreaks around the world, 2023 could turn out to be one of the worst years on record for the infection. The World Health Organization (WHO) has said that , with outbreaks being reported in the Americas, Asia and Africa. Despite its prevalence and the threat it poses, the existence of different types of the virus and the way that they provoke immunity or complications mean that developing an effective vaccine has been notoriously difficult.
As of the end of July, , with Brazil, Bolivia, Peru and Argentina the worst-hit countries. In the Americas, . If the situation carries on as it is, the WHO has warned that there , putting it close to the record .
Dengue has no specific treatments and usually resolves over one to two weeks. However, it can cause severe symptoms, known as dengue fever, and can sometimes be life-threatening. A lack of treatment makes developing an effective vaccine all the more vital, says at the University of São Paulo in Brazil. A three-dose vaccine called Dengvaxia is approved by both the US Food and Drug Administration and the European Medicines Agency. But it isn’t widely used for several reasons, says at the London School of Hygiene & Tropical Medicine.
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The main problem is that the dengue virus has four serotypes, which are groups within a single species of a microorganism that have different surface structures. For dengue, these are called dengue-1, 2, 3 and 4. Amid the ongoing outbreaks, all four serotypes are circulating at different levels in different countries, with these regularly fluctuating in their prevalence.
Being infected with any serotype can result in lifetime immunity to that specific serotype, but it can also lead to complications if that person is later infected with another serotype, says Hibberd. However, if the same person then goes on to be infected again with one of the other two serotypes, they usually aren’t at the same risk as they were with their second infection, he says.
Dengvaxia is based on the yellow fever virus that has been made to express proteins from all four dengue serotypes. For unknown reasons, . When Dengvaxia is given to people who have never been exposed to any dengue serotype, it acts like their first infection. If that vaccinated person then becomes infected with a serotype that isn’t dengue-4, they can have a far more severe reaction than if they hadn’t been vaccinated.
In 2016, the Philippines was the first Asian country to approve Dengvaxia and . A year later, it emerged that haven’t previously been infected but go on to be infected after vaccination. Dengvaxia was subsequently banned in the country.
The WHO now recommends that if it is administered after a blood test that shows someone has previously been infected with dengue, so the vaccine wouldn’t be their first brush with the virus. Having the vaccine be their second brush with the virus, after an infection, is not thought to be an issue. “If you had a natural dengue infection previously, then had the Dengvaxia vaccine administered, you would boost that original protection and also generate a more protective response against all three remaining serotypes [not dengue-4],” says Hibberd.
The serotypes aren’t the only issue. Even against dengue-4, Dengvaxia becomes markedly less effective around a year after its final dose, says Hibberd. This, coupled with the need to administer a blood test pre-vaccination and the fact that it requires three doses, has led to a very low uptake, he says.
Producing just one vaccine that has an equal response to all four serotypes is really difficult, says at Johns Hopkins University in Maryland. One experimental vaccine is in the final stages of clinical trials and shows some promise, she says.
It is made up of all four dengue serotypes, which have been genetically edited to not cause serious illness. Compared with Dengvaxia, it contains more genetic material of the four serotypes and is therefore thought to elicit a stronger immune response against them all.
Early results from a trial in Brazil published last year showed that . It is unclear how effective it is against the other two serotypes as these weren’t widely circulating in the country at the time of the study.
It is also too early to tell how long this vaccine’s protection lasts, says Durbin, who was involved in some of its trials. Nevertheless, it is just a single dose and so would be far easier to administer than Dengvaxia if approved, she says, adding that more results are expected in the next year or two.
Durbin hopes that this vaccine could play a major role in tackling dengue, which could be particularly important if climate change makes some countries more suitable habitats for the mosquitoes that spread the virus. “In 10 years’ time, I think we’re still going to be seeing a lot of dengue fever, but I also think we’ll be vaccinating the vast majority of people who need it,” she says.
