The final-stage testing of a potential coronavirus vaccine developed by the National Institutes of Health (NIH) and American bio-tech company Moderna began on Monday across the US.
Thirty-thousand people are taking part in various locations, as they are given either a real dose or a fake one without being told which is which.
"I'm doing it because again, I'm a retired healthcare worker and I understand the challenges COVID-19 has caused our community, state and the whole country," said study participant Karen Juser, a retired nurse.
Juser received an injection in Binghamton, New York.
It will be months before results trickle in, and there is no guarantee the vaccine will ultimately work against the scourge that has killed about 650,000 people around the world, including almost 150,000 in the US, the world's worst-affected country.
Scientists set speed records getting a made-from-scratch vaccine into such massive testing just months after the coronavirus emerged. But they stressed that the public shouldn't fear that anyone is cutting corners.
"This is a significant milestone," NIH Director Francis Collins said after the very first test injection was given, at 6.45 am in Savannah, Georgia. "It comes at a remarkably rapid pace compared to the usual pace for vaccine preparation."
After volunteers get two doses a month apart, scientists will closely track which group experiences more infections as they go about their daily routines, especially in areas where the virus is spreading unchecked.
The answer probably won't come until November or December, cautioned Dr Anthony Fauci, NIH's infectious-diseases chief.
Several other vaccines made by China and by Britain's Oxford University began smaller final-stage tests in Brazil and other hard-hit countries earlier this month. But the US requires its own tests of any vaccine that might be used in the country.
The final U.S. study of the Oxford shot is set to begin in August, followed by a candidate from Johnson & Johnson in September and one from Novavax in October.
Pfizer Inc. plans its own 30,000-person study this summer.
In recent weeks, more than 150,000 Americans filled out an online registry signalling interest, Collins said.