Upstate researchers are working to tackle the global health crisis that dengue virus (DENV) poses, and their efforts were featured in a recent issue of Nature Microbiology. Their paper details their results of an experimental human challenge study; showing how they successfully infected volunteers with a weakened version of DENV, resulting in mild-to-moderate symptoms and a robust immune response. Being able to safely infect volunteers with DENV using a challenge model such as the one described in this study will allow researchers to test potential vaccines or antivirals on a smaller scale before time-consuming and expensive testing in the field. Experts hope this could finally lead to a broadly protective dengue vaccine, which has yet to be developed for a disease that impacts over 400 million people across the globe each year. 

Stephen Thomas, MD (left) and Adam Waickman, PhD (right), who lead an experimental human challenge study in their efforts to find treatments and an effective vaccine for the dengue virus.

Stephen Thomas, MD and Adam Waickman, PhD, along with many other Upstate researchers from the Institute of Global Health have made dengue a major focus; working to solve the difficult problem of developing an effective vaccine for the disease. Partnering with the US Army, they conducted a trial infecting nine participants with a version of the virus developed and manufactured using strict processes with oversight by the FDA. “The US Army viruses we use in these studies have been weakened to make sure our experiments are safe,” says Thomas. 

“Dengue is a major global public health problem. It is also a problem for travelers and military personnel,” Thomas explains. “We have very few tools available right now to prevent infection or treat the disease which occurs in some people after they are infected.” 

There are several challenges to creating a vaccine for the disease that, according to the CDC, about 4 billion people around the world are at risk of contracting. A main hurdle is that there are four distinct DENV serotypes, which means that a broadly protective vaccine must generate balanced immunity against all four viruses simultaneously. In addition, animal models of dengue fail to recapitulate many of the features of the human disease, meaning conventional preclinical animal studies are often poor predictors of the potential clinical benefit of candidate DENV vaccines and other countermeasures. 

In the Nature paper Waickman and Thomas point to the fact that the strain they used produced lab results closer to those typically seen in naturally occurring dengue infections compared to previous trials. The participants only reported feeling mild to moderate symptoms, still mostly able to go about their daily activities.  

There are still a few challenges to face in their efforts to create an effective human model; one being the delivery of the virus to patients. The presence of mosquito saliva and/or salivary proteins have been shown to impact how the virus develops in humans; this trial injected the participants. “Delivering our viruses with a mosquito is possible but has a number of complexities associated with it,” says Thomas. 

Read the full paper on this study in Nature here. You can also learn more about the efforts of Upstate researchers to fight dengue at their upcoming research conference “The Second Annual Dengue Endgame Summit”, being held this summer. Find more details about the event and how you can attend here.