Two new studies in monkeys offer more signs, though very preliminary, that humans may develop immunity after being vaccinated or recovering from COVID-19. Using a series of prototype vaccines—ones used for medical research only and not intended for human use—researchers found that the interventions prevented rhesus macaques from becoming infected by the novel coronavirus. In a related experiment, macaques that tested positive for the virus were protected from re-infection when they encountered it a second time. The findings were reported in the journal Science on May 20.

“These data suggest that natural protective immunity to this virus indeed exists,” says Dan Barouch, a coauthor of the two studies and the director of the Center for Virology and Vaccine Research at the Beth Israel Deaconess Medical Center in Boston. “These studies are good news and overall they increase our optimism that the development of a vaccine is likely going to be possible.”

At this point, little is known about how our immune systems respond to COVID-19. While researchers have recently reported promising evidence that multiple parts of the immune system are roused in people with mild cases of COVID-19, it remains to be seen whether that response will give them strong or lasting protection against the novel coronavirus in the future. There also hasn’t been much data on the potential long-term immunity of people who had severe cases of COVID-19. Further, it’s not yet certain whether a vaccine will indeed be able to prevent people from catching COVID-19.

As a first step to addressing these questions, Barouch and his colleagues infected nine monkeys with the virus that causes COVID-19, SARS-CoV-2. The animals all developed pneumonia and then recovered within a few days. Thirty-five days after the monkeys had been infected, the researchers exposed the animals to the virus for a second time. Although the scientists did detect low levels of the virus in the monkeys’ noses on the following day, it was soon quashed and the animals experienced few or no symptoms. The findings, Barouch and his colleagues wrote, indicate that after their initial recovery the monkeys had “near-complete protection” from subsequent infections.

One important caveat of the new study is that macaques do not perfectly reflect how the human immune system behaves. For one thing, none of the monkeys that Barouch and his colleagues infected with the novel coronavirus became seriously ill, so they don’t represent what happens in severe cases of COVID-19 in people. “Any extrapolations for humans need to be done very carefully and ultimately will require large scale clinical trials,” he says.

For the second experiment, the team gave groups of macaques six different experimental vaccines that included DNA coding for the spike-shaped protein on the surface of SARS-CoV-2. This protein helps it infect cells and seems to be the part of the virus that the immune system responds to most strongly. The vaccines train the immune system to recognize this spike protein when faced with the actual virus.

Several weeks later, the researchers dosed the monkeys with SARS-CoV-2. “We observed that the vaccines offered a substantial degree of protection,” Barouch says. He and his colleagues were unable to detect the virus in the nose or lungs of eight of the 25 monkeys after their immunization, while the others had very small amounts of SARS-CoV-2. Some of these prototype vaccines were more effective than others; monkeys in the groups that received vaccines containing the virus’s entire spike protein fared better than their fellows.

The researchers also examined how the macaques’ immune systems responded to SARS-CoV-2 and to the vaccines. “Both the natural infection as well as the vaccine induced a range of immune responses,” Barouch says. His team observed several kinds of antibodies in the animals’ blood, including neutralizing antibodies that glom onto the virus to prevent it from infecting cells, and several kinds of T cells, which rouse the immune system and kill infected cells.

After vaccination, the more of these neutralizing antibodies a monkey produced, the better protected they were from SARS-CoV-2. This indicates that scientists testing vaccines for COVID-19 can use antibody levels as a measure to determine if a particular candidate is likely to be effective in people.

The vaccines that Barouch and his team used for the experiment were created for research purposes only. However, they plan to use what they learned in these studies to help develop vaccines in humans. Currently, they are working with Johnson & Johnson to develop a separate vaccine candidate that they hope to bring to clinical trials. Meanwhile, two vaccine candidates developed by the Beijing-based company Sinovac Biotech and Oxford University that are now being tested in people have reportedly given macaques partial protection from the novel coronavirus.

The new findings do not address how long protective immunity to COVID-19 might last. But they do suggest that the process of developing a COVID-19 vaccine could be relatively straightforward. “There is no clinically licensed HIV vaccine, and one of the reasons is that for HIV there is no evidence of natural protective immunity,” Barouch says. No one with HIV actually clears the virus from their bodies. It is much easier to develop a vaccine if there’s evidence that people have some sort of immunity after they recover from an infection. “That shows that the human immune system can indeed fight off the virus.”