Dengue vaccine candidate protects fully in controlled human challenge trial

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Findings, process can further vaccine quests, researchers say

An experimental vaccine against dengue completely protected the 21 volunteers  who received it and were subsequently exposed to the virus, while the 20 volunteers who received a placebo instead developed infection after exposure, a study published today in Science Translational Medicine found. Researchers who conducted the human challenge trial say the results bode well for the possibility of protection against the mosquito borne disease in real life conditions, and for the development of other vaccines.

The vaccine candidate called TV003, developed by scientists at the National Institutes of Health, will now be tested among 17,000 volunteers in a trial that began in Brazil last month, researchers said. With plans to enroll all volunteers within the next year, and follow them through at least one season when dengue is prevalent, researchers said that if the vaccine is successful it could be registered as early as 2018.

In addition, researchers said the controlled human challenge model through which the candidate was tested could be applied to more efficiently test Zika vaccine candidates, as well as to learn more about that virus.

Dengue, a viral infection that can cause from no symptoms to mild fever, to debilitating fever and pain, and is life-threatening in its most severe form, has spread rapidly around the world in recent years, putting about half the world’s population at risk of infection, according to the World Health Organization. While early detection and medical care can lower the risk of death to under 1 percent, severe dengue remains a leading cause of death and illness among children in some countries. But the four strains of the virus, transmitted by the Aedes aegypti mosquito (that also spreads Zika virus and chikungunya) has complicated attempts to develop a safe and effective vaccine against it. While recovery from an infection delivers immunity against the infecting strain, it can also increase the severity of subsequent infections with other strains. A vaccine that confers immunity against one strain but is ineffective against others could raise the risks of serious illness in areas where multiple strains of dengue circulate, authors of the study released today noted. For that reason, all  five dengue vaccine candidates currently in development combine all four strains. Only one of those, the CYD-TDV vaccine, developed by Sanofi Pasteur has been tested in large, on-the-ground clinical trials. Its efficacy has been limited, showing protection for less than 60 percent of those receiving it and only 35 percent of those who had never been infected with dengue, while follow up data showed that children under nine receiving it who were subsequently infected had a greater risk of severe illness requiring hospitalization than children who had received a placebo.

Testing the NIH candidate in a controlled environment, with 41 volunteers exposed to a mild strain of dengue that produced little or no symptoms, reduced both risks and the investment in determining its efficacy, researchers said. While all of the volunteers who received the placebo showed evidence  of the virus circulating in their blood, 80 percent developed a rash, and 20 percent showed a temporary drop in white blood cell counts, none of the volunteers who received the vaccine candidate showed  evidence of virus, rash, or drop in white blood cell counts, researchers said.

Calling the results “very promising,” while noting they would need to be confirmed in the large-scale  trial that began last month, researchers emphasized that the trial also had been valuable in demonstrating how vaccine and treatment candidates can be screened to ensure that only the most promising products are tested in endemic areas among large study populations.

Authors of the study, “The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model” was authored by Dr. Beth D. Kirkpatrick of the University of Vermont Vaccine Testing Center, Dr. Stephen Whitehead of NIH, and Dr. Anna Durbin of Johns Hopkins Bloomberg School of Public Health.

 

 

 

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