The human challenge of Dengue protection

A live attenuated Dengue vaccine is completely protective in a human challenge model

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Vaccine development is a long and meandering road, in which heartening results are not easy to come by. This explains the generalized optimism and hope elicited by the announcement of positive results for the Dengue live attenuated vaccine TV003 in Science Translational Medicine. That, and the fact that Dengue and Zika viruses are similar and, thus, this could inform Zika vaccine development efforts. The news was covered in STAT, WIRED, CNN, NBC and many others.

Dengue fever affects approximately 400 million people a year, most of which live in developing countries in the Earth's tropics. It is transmitted by Aedes mosquitoes, mainly A. aegypti, which also carry Zika virus, and which are spreading into Southern Europe and the US.

Female Aedes mosquito caught in the act (of feeding)

Dengue fever is caused by Dengue virus (DENV), of which there are four serotypes, and prior exposure to one does not protect from infection with another. In fact, subsequent Dengue exposure is a risk factor to develop a more severe disease known as Dengue hemorraghic fever, and you can imagine that in endemic areas of the world, where most serotypes coexist, this is a rather frequent event.

TV003 is a live but attenuated DENV that induces a strong antibody and cellular immune response after just one dose. In order to shortcut the long road of field trials, Durbin and colleagues performed a controlled human challenge trial. Healthy volunteers were inoculated with a DENV-2 virus strain known to cause mild disease, six months after having received vaccine or placebo. All vaccinated individuals were protected from the challenge, and everybody in the control group showed signs of disease. This promising result has spurred the launch of a large-scale phase 3 vaccine trial in Brasil, which will enroll almost 17,000 people.

Controlled human challenge studies can be performed with agents that cause mild disease and have been very useful in vaccinology. Their use, for example, in the context of malaria vaccine research is well known. Now, researchers are hoping to use the same setup for pilot vaccine trials against (closely related) Zika virus, in order to speed up the pace of discovery. Godspeed!

Nonia Pariente

Chief Editor, Nature Microbiology

I come from a mid-sized city on the northwestern coast of Spain. My interest in science initially took me to Madrid, where I finished university and received a PhD in molecular biology. In Madrid, I studied RNA virus evolution and new antiviral strategies with Esteban Domingo. I then moved to UCLA, where I focused on developing lentiviral vectors for gene therapy in Irvin Chen’s laboratory. In 2007, I made the plunge from bench to desk and joined the EMBO Reports editorial team as Reviews Editor, becoming Scientific Editor two years later and Senior Editor in 2012. At EMBO Reports, I was responsible for microbiology and immunology, among other areas, and spent many years expanding my understanding and love for all things microbial. In the summer of 2015, I joined the Nature Microbiology editorial launch team, handling all things related to virology and mycology (and for a brief while parasitology) and -after a couple of stints covering microbiology at Nature- I became the Chief Editor of Nature Microbiology in 2019. I look forward to interacting with the community and providing a venue to publish the most important advances in the field.