They said so-called "human challenge trials" or "controlled infection trials" were of "vast importance" in speeding up the testing of the vaccines in development around the world.
"If challenge trials can safely and effectively speed the vaccine development process, there is a formidable presumption in favor of their use, which would require a very compelling ethical justification to overcome," the scientists wrote in the letter to Dr. Francis Collins, director of the US National Institutes of Health (NIH).
It urged the US government to undertake immediate preparations for human challenge trials, "including supporting safe and reliable production of the virus and any biocontainment facilities necessary to house participants."
The letter said human challenge trials -- in which volunteers are deliberately exposed to the pathogen under controlled conditions -- can provide information months before conventional efficacy trials, in which candidates receive a vaccine or control and resume their normal life, with the assumption that they may be eventually exposed to the virus.
More than 2,000 challenge trial volunteers also signed the letter published by 1Day Sooner, an organization advocating on their behalf.
Adrian Hill, director of the Jenner Institute at the University of Oxford in England, and signatory of the open letter, wrote in a statement that "collaborative human challenge studies should be feasible and informative in the coming months."
Oxford's Jenner Institute is working with 1Day Sooner to produce a Covid-19 human challenge virus and Hill said it had "considerable potential" for helping to accelerate vaccine development and optimize vaccination approaches.
The World Health Organization (WHO) issued guidance in May saying challenge studies can be "substantially faster" and more effective than other methods, in part because fewer participants need to be exposed to experimental vaccines and because they can be used to compare potential vaccines.
Challenge trials were used in early research with smallpox, yellow fever and malaria, which changed the course of global public health, according to WHO.
Over the past 50 years, tens of thousands of consenting adult volunteers have safely undergone such trials under the oversight of research ethics committees, WHO reported.
It said controlled infection trials could be ethically acceptable if they met certain criteria. These include choosing young and healthy adults as participants, starting with low doses, ensuring public engagement, and providing high-quality care and close monitoring.
The notion of a human challenge trial for Covid-19 was jump-started by a March 31 article in the Journal of Infectious Diseases, which made the case that the nature of the global emergency warranted consideration of unconventional approaches.
Co-authored by Nir Eyal of Rutgers, Marc Lipsitch of Harvard, and Peter Smith of the London School of Hygiene & Tropical Medicine, the piece concluded that while a human challenge study would not be without risks, "every week that vaccine rollout is delayed will be accompanied by many thousands of deaths globally."
But members of the NIH's Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV) Vaccines Working Group said earlier this month that challenge trials would not speed up vaccine development.
In a commentary published in the New England Journal of Medicine, ACTIV members wrote that using controlled human infection models to support vaccine development requires "essential criteria" to limit the risk for participants and could take "one to two years."
"A single death or severe illness in an otherwise healthy volunteer would be unconscionable and would halt progress," they wrote.
They said it would be unethical to organize an experiment in which people were deliberately infected unless there were a rescue therapy -- a treatment that can save lives -- which does not exist for coronavirus.
"Large, randomized, controlled trials of SARS-CoV-2 vaccines are currently the most efficient, generalizable, and scientifically robust path to establishing vaccine efficacy," the authors concluded.