AsianScientist (Dec. 28, 2015) – Earlier this month, Dengvaxia, the dengue vaccine developed by pharmaceutical giant Sanofi, won regulatory approval for use in Mexico—the first time that any vaccine for the mosquito-borne viral disease has been approved. Last week, it was approved in the Philippines as well.
Vaccines for the related yellow fever and Japanese encephalitis viruses have been around since the 1930s. But dengue, a much more genetically diverse pathogen with four distinct viral serotypes, has proved difficult to crack.
After more than seventy years and perhaps billions of dollars spent on vaccine development, having one available for use is certainly a long-awaited piece of good news. Still, there are limits to the vaccine’s effectiveness, and most scientists would agree that it doesn’t yet represent a global solution.
Not quite a silver bullet
It’s quite clear that Dengvaxia protects recipients against severe dengue. In advanced-stage clinical trials carried out in Southeast Asia and Latin America, it dramatically reduced hospitalizations for the disease by about 80 percent.
The findings then get more complex. The vaccine was reasonably effective at preventing any form of disease caused by three of the four virus serotypes. But serotype 2 threw a spanner in the works—here, the vaccine only managed to reduce disease by 35-50 percent. This affected overall vaccine efficacy, which came in at about 65 percent (for comparison, the yellow fever vaccine is effective in about 99 percent of recipients). This also raises questions about whether the vaccine should be deployed in areas where serotype 2 is dominant.
In many endemic countries, children under the age of nine are more likely to develop severe dengue. Unfortunately, the vaccine turned out to be least effective in this high-risk age group. Also of possible concern are results from a follow-up study done three years after the vaccine was administered, which found it to be associated with an increased risk of hospitalization for dengue in children under nine.
If this is confirmed, it’s possible that the vaccine may be eliciting only a partial or temporary antibody response in younger children. Such a response would not only be ineffective at neutralizing viruses during a subsequent natural infection, but could also enhance the infection by allowing viruses to more easily infect immune cells, thus putting the individual at a higher risk of severe disease.
Reassuringly, however, the vaccine did not increase the risk of life-threatening dengue complications such as dengue shock syndrome, in which the loss of plasma through leaky blood vessel walls causes systemic shock from low blood volume.
Researchers are continuing to monitor the situation over the longer term to see if the increased risk of hospitalization was a chance result, or if the trend continues. Meanwhile, the vaccine has only been approved for use in people aged 9-45.
One more tool in the toolbox
Finally, the vaccine was more effective in people who have had a previous dengue infection than in people who have never been exposed. This suggests that it does a better job of boosting naturally acquired immunity, rather than of stimulating an immune response from scratch. Thus, it may be of limited value for countries with lower rates of dengue, and for travelers from non-endemic regions whose immune systems have never seen the virus.
It’s true that there is no such thing as a perfect vaccine. In addition, dengue takes a heavy toll on healthcare systems—with no antiviral treatments available, patients who show warning signs of progressing to severe disease have to be hospitalized and constantly monitored, with careful administration of fluids to prevent the development of shock.
Thus, even a vaccine with a sub-optimal level of effectiveness may make sense in highly endemic countries. But dengue’s complex interaction with the human immune response means that there is no clear-cut, one-size-fits-all decision.
These considerations, together with the as-yet-unannounced price of the vaccine, will affect where and how widely it is adopted. In Mexico, members of the public will be able to buy the vaccine on their own, but it’s still unclear if the government intends to launch a vaccination program on a national scale, which would have the biggest impact on reducing transmission.
Sanofi is in the process of seeking regulatory approval in more countries in Asia and Latin America, but it is likely to be a while before dengue can be deemed a vaccine-preventable disease. In the meantime, research into antivirals, clinical management strategies, and mosquito control continue.
This article is from a monthly column called The Bug Report. Click here to see the other articles in this series.
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Copyright: Asian Scientist Magazine; Photo: Sanofi Pasteur/Flickr/CC.
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