Yellow fever, a mosquito-borne hemorrhagic disease that is common in South America and sub-Saharan Africa, annually infects about 200,000 people and causes an estimated 30,000 deaths. While there is a vaccine, side effects make it inappropriate for some people, and there are no approved treatments for the disease.

Now an international team of researchers led by Professor Ram Sasisekharan may have developed one, using an innovative and unusually efficient approach. Their drug, an engineered monoclonal antibody, has shown success in early-stage clinical trials in Singapore.

Monoclonal antibodies are lab-­produced molecules that mimic the function of human antibodies in targeting foreign proteins for attack by the immune system. They hold promise for treating a variety of infectious diseases, but it usually takes several years to develop and test them. The MIT-led researchers demonstrated that they could design, produce, and begin clinical trials of their antibody drug within nine months.

“Traditional drug development processes are very linear, and they take many years,” Sasisekharan says. “If you’re going to get something to humans fast, you can’t do it linearly, because then the best-case scenario for testing in humans is a year to 18 months.”

Sasisekharan’s group was able to compress the antibody development timeline by performing many of the necessary steps in parallel, using analytical techniques to address regulatory risks associated with drug safety, manufacturing, and clinical study design.

The parallel process could also be used to develop new treatments for covid-19, says Sasisekharan, a professor of biological engineering. A covid-19 antibody treatment developed in just four months using this approach is now being tested in a clinical trial in Singapore.

“The mindset in the industry is that it’s like a relay race. You don’t start the next lap until you finish the previous lap,” Sasisekharan says. “In our case, we start each runner as soon as we can.”

Because there is a vaccine available for yellow fever, the researchers were able to perform a type of clinical trial known as a challenge test. They vaccinated volunteers and then, 24 hours later, gave them either the experimental antibody drug or a placebo. Two days after that, they measured whether the drug cleared the weakened viruses that make up the vaccine. After treatment, the virus was undetectable in blood samples from people who received the antibodies. The results were published in the New England Journal of Medicine in July.