Before Sanofi Pasteur distributed its dengue vaccine, Dengvaxia, there were some concerns that it would actually make people sicker. A new study from top universities has found this to be the case in some areas.

Researchers from Johns Hopkins Bloomberg School of Public Health, Imperial College London and the University of Florida have confirmed critics’ suspicions that Sanofi Pasteur’s dengue vaccine, Dengvaxia, was too good to be true: in a study published in Science, the collaboration demonstrates that despite a promising 60% reduction in infections, many inoculated young people eventually become sick again, and more seriously so.

Their transmission model explains that in areas of high virus transmission, Dengvaxia use is a net benefit, as it reduces hospitalizations and severe cases by 20 to 30%. However, under moderate transmission, hospitalizations of vaccinated children increased three years after vaccination, compared to unvaccinated children. The researchers linked it seronegativity: children who had never been infected and caught the virus after inoculation drove the rise in hospital visits.

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Figure 1. Children who have never had dengue before being vaccinated are at elevated risk of being hospitalised.

Figure 1. Children who have never had dengue before being vaccinated are at elevated risk of being hospitalized if they are infected afterwards.

A second dengue infection is often much more severe than the first, and because the vaccine acts like a silent natural infection, any subsequent infection is immediately as serious as a second one. Generally, vaccines are not 100% effective, so it is possible that patients will still come down with the fever; and in the case of those inoculated with Dengvaxia, their symptoms will be much more serious and requiring of emergency medical care.

Dr. Scott Halstead, a former US Army scientist who told STAT News,

I do not believe … anybody should be going forward using this vaccine without testing the individual recipient to be sure they’re already seropositive [that is, that they’ve already had dengue]. Because that’s the group that can benefit from this vaccine.”

Accordingly, the World Health Organization is recommending that children younger than nine years old are not vaccinated because they are less likely to be seropositive. This follows its warning earlier this year that the vaccine should only be administered in countries where dengue is more than 50% prevalent.

Figure 2. Dengvaxia would be most beneficial in red areas.

Figure 2. Dengvaxia would be most beneficial in red areas.

As a result of the controversy, Sanofi Pasteur collected a measly €1M in second-quarter sales that pushes the company’s €200M annual sales goal out of reach. Even so, Sanofi Pasteur is moving forward with its campaigns in Latin America and Asia, which are underpinned by Dengvaxia. This may be spurred by increased pressure from Takeda, whose dengue vaccine just entered Phase III last week.

Though Sanofi Pasteur is struggling to rescue Dengvaxia, hope is not lost for dengue vaccines. Other European companies in biotech are working on their own dengue vaccines; Excivion is taking it a step further, aiming for  a dual one that will also target Zika. Instead of attacking the virus, other biotechs like Oxitec are focusing on the vector and rolling out genetically modified mosquitoes to stem its spread. Even if it seems impossible to develop a perfect vaccine, incorporating any vaccine into a multipronged approach will surely reduce the threat of dengue.


Featured Image: mycteria/Shutterstock.com
Figure 1: Jarun Ontakrai/Shutterstock.com
Figure 2: Alex Mit/Shutterstock.com

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