Scientists reported on Wednesday that they think they have found the “final puzzle piece” for a dengue vaccine that might, at last, be able to stop the deadly mosquito-borne virus that has infected billions since the early 19th century.

The experimental vaccine, developed by the National Institutes of Health, was tested in a small, randomized, double-blind trial on 41 healthy volunteers. Each participant received either a single shot of an experimental vaccine or a placebo and were then infected with a mild form of the virus six months later. All of the 20 people in the placebo group came down with rashes, low white blood cell count and other symptoms of the disease, while none of the 21 vaccinated volunteers became sick and did not have evidence of infection in their blood.

The results, reported in Science Translational Medicine, were so promising that large-scale Phase 3 tests of the vaccine already started in Brazil on Feb. 22. The target enrollment is 17,000 adults, adolescents and children with an estimated completion date of 2018. In a conference call with reporters this week, researchers — who tend to pepper their description of studies with talk of limitations and caveats — were uncharacteristically optimistic that the vaccine will be successful.

“Knowing what we know about this new vaccine, we are confident that it is going to work,” said Anna P. Durbin, an associate professor at the Johns Hopkins Bloomberg School of Public Health, which led the small study.

Her colleague, Beth Kirkpatrick, a professor of medicine at the University of Vermont, which also participated in the trials, said that “the results of this work are very straightforward and quite conclusive.”

“The bottom line is that the vaccine appears to be 100 percent efficacious,” Kirkpatrick said.

The promising results bode well for efforts to develop a Zika vaccine. Zika and dengue are in the same family of viruses, and NIH officials have said they hope to cut the timeline for having a Zika vaccine by building on their work on dengue.

Teams of researchers from both the government and industry have been working on developing a vaccine for the mosquito-borne virus for nearly 100 years. Dengue fever is one of the world’s virulent infectious diseases, with more than 400 million people becoming infected each year. While most develop only few or no symptoms, 2 million develop the most dangerous form of the virus and 25,000 die from it.

Dengue has been a particularly tricky target because of unique characteristics of the pathogen. There are four strains circulating in the world, and antibodies for each of the strains interact with each other in such a way that if a vaccine does not protect against all forms simultaneously, it could backfire and put a patient at risk of severe disease if exposed to the other types. In the worst case scenario, those receiving a faulty vaccine could go into dengue hemorrhagic shock, which is marked by bleeding, low levels of platelets and leakage of blood plasma, and die.

Human challenge trials like this one are an extremely efficient way for scientists to tell whether a particular vaccine is effective, but they are rarely conducted because of the ethical dilemma of the risk it places on volunteers who are purposely exposed to a virus. Steve Whitehead, a scientist at the National Institute of Allergy and Infectious Diseases and a co-author of the dengue paper, said that challenge trials have been used in the past for malaria, cholera, norovirus, flu and other diseases “for which there’s really urgent, urgent need to move the field forward over time.”

Whitehead and the other researchers said that in the case of dengue, the testing was warranted because they knew that the vaccine appeared to be effective at preventing dengue 1, 3 and 4 viruses through previous testing but needed to learn more about its impact on dengue 2 before proceeding to larger trials that could take three to 10 years and cost tens of millions of dollars.

They added that this type of test could also be useful for Zika, because we still don’t know basic things about the virus, such as how long it stays in the blood. “We see a Zika challenge model as really beneficial for not only vaccine development,” Durbin said, “but also to learn more about Zika itself.”

NIH officials have said that the same group of scientists working on dengue has already come up with some vaccine candidates for Zika that should be ready for small human tests this summer. John Mascola, who directs the NIH Vaccine Research Center, told The Washington Post that making a vaccine for Zika “should be quite feasible” based on what we know about its structure and DNA.