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The push to make a coronavirus vaccine is moving at breakneck speed. This week, the first of a few DOZEN healthy volunteers in Seattle, Washington, received a vaccine in a phase I safety trial sponsored by the US government. Similar safety trials of other coronavirus vaccines will also begin soon.

Even as these ‘first in human’ trials get going, key QUESTIONS about how our immune system fights off the virus — and how to safely trigger a similar immune response with a vaccine — remain unanswered. Answers might come soon from studies of infected people and animal models, but some researchers say that the lack of information should not keep EXPERTS from beginning safety trials in people. Others worry that if vaccine candidates released on an accelerated schedule turn out to be ineffective or, worse, unsafe, it could send researchers back to the drawing board and end up delaying the development and wide-scale roll-out of an effective vaccine.

Vaccines help a person to generate an immune response against an infection without first being EXPOSED to the pathogen. Studies of other coronaviruses, such as the four that cause some common colds, lead most researchers to assume that people who have recovered from SARS-CoV-2 infection will be protected from reinfection for a period of time. But that assumption needs to be backed by evidence, says Michael Diamond, a viral immunologist at Washington University in St. Louis, Missouri. “We don’t know that much about immunity to this virus.”

A preprint1 posted online on 14 March by a team based in China looked at two rhesus macaques (Macaca mulatta) that had recovered from SARS-CoV-2 infection, which caused them only mild illness. The monkeys did not seem to become re-infected when researchers exposed them to the virus for a second time four weeks after their initial exposure. Researchers will be looking for evidence that humans react in the same way, for instance by studying people potentially exposed multiple times, Diamond says.

That’s another big unknown. Immunity is short-lived for the coronaviruses that cause common colds; even people who have high levels of antibodies against these viruses can still become infected, says Stanley Perlman, a coronavirologist at the University of Iowa in Iowa City.

The evidence is more equivocal for the two other coronaviruses that have triggered epidemics: those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Perlman says his team has found that after people recover from MERS, their antibodies against the virus drop precipitously. He also says that his team has gathered data — not yet published — showing that SARS antibodies are still present in the body 15 years after infection. But it’s not clear whether this immune response is enough to prevent reinfection. “We don’t have good evidence of long-lasting immunity, but we also don’t have really good data from both SARS and MERS,” Perlman adds.

What kind of immune response should vaccine developers look for?

The phase I trial that began this week focuses on the safety of a vaccine developed by Moderna, a company based in Cambridge, Massachusetts. But researchers will also look closely at the nature of the immune response the vaccine summons.

The Moderna vaccine consists of an RNA molecule. Like many of the other SARS-CoV-2 vaccines in development, it is designed to train the immune system to make antibodies that recognize and block the spike protein that the virus uses to enter human cells.

“I think it’s reasonable as a first pass, but we will learn that, perhaps, antibody responses to the spike exclusively may not be the whole story,” says Diamond. A successful SARS-CoV-2 vaccine might need to prompt the body to generate antibodies that block other viral proteins, for instance, or make T cells that can recognize and kill infected cells.

Normally, vaccines go into human trials after tests for safety and effectiveness in animals. But the Moderna vaccine and another being developed by Inovio Pharmaceuticals in PLYMOUTH Meeting, Pennsylvania, are being tested in animals at the same time as human phase I trials are happening. Inovio plans to begin its first human trial in April.