Encouraging signs in the race to develop a COVID-19 vaccine have Minnesota health officials planning for some tough decisions ahead when the demand for shots far outpaces the limited initial supply.

While the state has experience in rationing scarce medical supplies — developing prioritization plans for the H1N1 swine flu vaccine in 2009, and for the antiviral remdesivir to treat COVID-19 earlier this year — health officials said the level of vaccine distribution amid this pandemic will be unprecedented.

“It will be a challenge,” said Kris Ehresmann, state infectious disease director. “We need to vaccinate the entire global population.”

Minnesota is one of four states recently invited into a pilot program by the U.S. Centers for Disease Control and Prevention to begin planning for the national distribution of COVID-19 vaccines.

More than 150 vaccine candidates have emerged since the discovery late last year of SARS-CoV-2, the novel corona­virus that causes COVID-19. The virus has caused 56,560 known infections and 1,616 COVID-19 deaths in Minnesota as of Monday and is spreading through the U.S. at a rate of 1,000 deaths and 100,000 cases per day.

“It’s a very sobering point in the pandemic for all of us,” state Health Commissioner Jan Malcolm said.

Five vaccine candidates have reached Phase 3 clinical trials, which are the final stages in research before the U.S. Food and Drug Administration and regulatory agencies in other nations decide whether they are safe and effective enough for mass use. Moderna Inc. is already manufacturing doses of its vaccine for U.S. distribution even though its Phase 3 trial in 30,000 people has only begun.

Others remain under development, including at Mayo Clinic in Rochester and the University of Minnesota in Minneapolis, and could be set for clinical trials next year.

“The prospect of a vaccine that ... has a beneficial effect on preventing or reducing illness in someone who gets SARS-CoV-2 disease is pretty strong,” said Dr. Andrew Badley, leader of Mayo’s COVID-19 research group.

Health officials also know that there won’t be enough doses to go around at first.

When remdesivir was first approved this spring as an antiviral treatment for hospitalized COVID-19 patients, the Minnesota Department of Health advised against giving limited initial supplies to the most severe patients at imminent risk of death. Instead, the state prioritized severely ill patients who hadn’t yet been placed on ventilators to breathe and were more likely to survive with the drug’s help.

When it comes to a vaccine, health care workers will likely be first in line given the risks of infection they face in working with COVID-19 patients. The state on Monday listed 6,425 health care workers as having suffered SARS-CoV-2 infections.

“Health care workers have to be at the top of the list,” said Michael Osterholm, director of the U’s Center for Infectious Disease Research and Policy. “We need them so badly.”

Who next? The elderly population would be one choice. People 70 and older make up only 9% of known infections in Minnesota but 80% of COVID-19 deaths.

Priority also could go to residents of long-term care who have suffered 76% of the state’s COVID-19 deaths, or to pregnant women at greater risk of complications.

Vaccinating young adults first could slow the spread of the pandemic. People in Minnesota 29 and younger make up 37% of known infections and have been associated with mass outbreaks in bars and social gatherings that have fueled a resurgence in viral activity this summer.

However, this age group has suffered only five COVID-19 deaths in Minnesota and is at the lowest risk for deaths and complications.

Consideration also needs to go to minorities who have higher levels of skepticism over vaccines in general but also worse COVID-19 outcomes, Osterholm said. In Minnesota, Black people make up 21% of known infections but less than 10% of the state’s population.

Osterholm said his center is planning to develop guidance to prioritize vaccination for minority groups and encourage their participation.

A measles outbreak in the Twin Cities in 2017 was largely confined to the Somali American community, in which vaccination rates were lower.

“Underserved populations [need to] get the kind of information that will allow them to make sound and helpful decisions about whether to get vaccinated or not,” Osterholm said. “Some of these are also the most disenfranchised populations in terms of looking at vaccine safety and use.”

Guidance will likely come from the CDC’s Advisory Committee on Immunization Practices on who to prioritize, but then states will have to act on it, Ehresmann said.

Minnesota was selected as one of four states providing planning advice to the CDC via a new pilot program because of its history of working with medical providers to create ethical treatment guidelines, Malcolm said. “This is something Minnesota has really been leading the nation on for probably 20 years now.”

Not all COVID-19 vaccines will end up being the same, and that could further complicate prioritization plans if studies show that some versions work better in certain demographic groups.

Proposed vaccines by Moderna and others seek to use genetic RNA material from the virus to coax the body into producing antibodies that fight off the infection. Others already in human clinical trials are based on more traditional approaches of using live or inactivated forms of the virus to produce an immune response.

The U is testing a vaccine in animals that coaxes the body’s protective T cells into clearing out any cells infected by the SARS-CoV-2 virus.

Mayo has four “homegrown” vaccine models under development, Badley said. He expects Mayo to announce partnerships with private manufacturers later this year and clinical trials in 2021.

A variety of approaches are needed, Badley said, because other viruses have shown resistance to certain vaccine types. Vaccines that tried to create an antibody response against HIV did not work.

“Different vaccine approaches augment different elements of the immune system,” Badley said. “As of today, we don’t know which ones of those are preferable. Until we have that knowledge, it makes sense to develop a variety of different approaches.”