Oct. 12, 2020 -- In 1976, when Army recruits in Fort Dix, NJ, fell ill from a virulent form of influenza, infectious disease doctor William Schaffner, MD, got his first lesson in the perils of pandemic planning. Lab tests revealed a strain genetically similar to the one that triggered the deadly 1918 Spanish flu pandemic. Although it hadn't spread beyond the Army post, the potential was frightening.
Schaffner, then a junior faculty member at Vanderbilt University School of Medicine, recalls that his mentor, pediatric virologist David Karzon, MD, traveled to the CDC in Atlanta and came back feeling out of sorts. The CDC presented its plan for mass vaccination, but it seemed more like a showcase than a quest for advice.
President Gerald Ford, who was in the middle of a contested primary campaign against Ronald Reagan, vowed to protect Americans. But months later, when the pandemic never arrived, the vaccination program came to be known as "the swine flu fiasco." By December 1976, vaccinations came to an abrupt halt. About 45 million Americans had received the "swine flu" vaccine against an H1N1 influenza strain known to circulate in pigs. About 450 of them developed a rare neurological condition called Guillain-Barré syndrome, but its connection to the vaccine is still debated.
In the aftermath, the CDC dissected each decision. Had the mass vaccination moved forward too rashly? Should they have paused to reconsider the plan? How could the nation's public health agency have done a better job of explaining its decisions?
Today, those questions still resonate. In the wake of more than 210,000 U.S. deaths from COVID-19, a vaccine could be a life saver. It promises a potential path back to normalcy. But as manufacturers ramp up production of COVID-19 vaccine candidates even before data emerge from phase III trials, the past holds lessons.
Whether a pandemic vaccine is a success or failure can be a matter of timing as well as of public perception, policymaking, and science. In 2009, when another pandemic strain of swine flu emerged, the Obama administration originally predicted that 160 million vaccine doses would be available by the end of October. It soon downgraded the projection to 40 million doses. As people stood in lines for flu shots, only 28 million doses were available. By January, the vaccine was plentiful, but the demand had slacked off.
"Don't overpromise and then underdeliver," concludes Schaffner, who is now professor of preventive medicine at Vanderbilt, medical director of the National Foundation for Infectious Diseases, and a liaison member of the CDC's Advisory Committee on Immunization Practices. "Better to underpromise and overdeliver."
Will COVID-19 Vaccine Delivery Be at "Warp Speed"?
The delivery of a vaccine against COVID-19 promises to be an astonishing feat. Operation Warp Speed has already funded about 800 million doses of vaccine from six manufacturers, including products that use new vaccine technologies. More than 80 million doses are expected by the end of the year, Moncef Slaoui, PhD, chief advisor of Operation Warp Speed, told the National Vaccine Advisory Committee on Sept. 23. The expert panel advises the Department of Health and Human Services on vaccination.
Moving at "warp speed" allows "a very rapid development without inappropriate corners being cut," Slaoui said. "All the risk taken is financial, logistical, and resourcing, but not on safety or efficacy." Bureaucratic obstacles have been loosened, removing the usual gaps between different phases of clinical trials and saving precious time, he said.
But even as technological advances led to lightning-fast vaccine development and manufacturing, some elements of the public health infrastructure remain stuck in the past. Recently, the American Immunization Registry Association asked members from state, county, and city health departments what tools they would use in conducting a COVID-19 vaccination campaign. While almost all (94%) said they would rely on an electronic immunization information system, or IIS, "paper" was the third most-common choice.
That might mean people receiving vaccines will sign paper consent forms, but vaccination programs might also use paper intake forms or vaccine reports. The information would need to be manually transferred to computers, says the group's executive director, Rebecca Coyle.
"We're having conversations now that we had 10 years ago with H1N1," when public health officials talked about improving the management of vaccine information, Coyle says. Funding for new systems didn't materialize, and public health departments have struggled just to maintain staffing. "As soon as the crisis is over, folks are on to the next crisis, whatever that might be."
The More Things Change …
There has been substantial progress, even with those drawbacks. Electronic health records are common now, enabling the mostly seamless transfer of vaccination data to state health departments. As of 2019, more than 116,000 health systems, pharmacies, and other sites were able to report doses electronically in real-time and query a consolidated database for information, Coyle says.
In 2018, 56% of U.S. adults had immunization information recorded in state information systems compared with just 22% in 2010, according to Coyle. That gives vaccinators a way to verify vaccination status, which is especially crucial because most of the leading COVID-19 vaccine candidates require two doses, and both doses must be the same vaccine.
Yet basic vaccine delivery challenges persist, says Rebecca Wurtz, MD, an infectious disease doctor and population health expert at the University of Minnesota School of Public Health in Minneapolis. In 2009, pharmaceutical company McKesson managed the distribution of almost 81 million H1N1 influenza vaccine doses to 90,000 sites, but public health officials struggled with the mechanics of designating priority groups and reaching out to them for vaccination while asking others to wait.
"I'm not sure there's much difference between 1976, 2009, and 2020-2021," she says. "The issues around organizing a massive distribution of a new vaccine are pretty similar."
Functionally, states shape the actual vaccination programs, deciding where vaccines can be administered and whether pharmacists can provide them independent of doctors or nurse practitioners. The Pfizer/BioNTech COVID vaccine candidate, one of the frontrunners currently in phase III trials, requires storage at -94°F, which may limit the sites that can offer it, if it receives approval. In fact, McKesson officials say that it will only distribute vaccines that are refrigerated or frozen, not "ultra-frozen."
As with other pandemics, COVID-19 will put the nation's public health capabilities to the test, says Harvey Fineberg, MD, chair of the Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats at the National Academies of Sciences, Engineering, and Medicine.
If, in a twist of fate, the 1976 swine flu had spawned a deadly pandemic, critics would have focused on the inability to provide enough vaccinations quickly enough, he says. "The big challenge in this era of COVID is going to be the capacity to actually deliver the vaccine to the populations who need to receive it," says Fineberg, who is currently president of the Gordon and Betty Moore Foundation, a Palo Alto, CA, based philanthropic organization established by the Intel co-founder and his wife.
Today's COVID Vaccine Response to Resonate
In 1978, Fineberg and Harvard University political scientist Richard Neustadt analyzed the first swine flu experience at the request of then-Secretary of the Department of Health, Education, and Welfare Joseph Califano. It was titled, "The Swine Flu Affair: Decision-Making on a Slippery Disease."
They reflected wistfully about the damage to the CDC's reputation, a government agency held in high esteem even during the post-Watergate, post-Vietnam rise in cynicism -- and how it impacted the view of public health.
"The innocence has gone, and with it clout, not for all time, as memories fade and new impressions take hold (if they do), but for some years. The loser is not likely to be CDC as such but rather new departures in preventive medicine," wrote Neustadt and Fineberg, who was then an associate professor in the Harvard School of Public Health.
Acceptance of influenza vaccination gradually grew, and in 2010, the CDC issued a universal influenza vaccine recommendation, stating that all Americans should receive the flu vaccine every year. In the 2018-2019 flu season, 45% of adults and 63% of children received a flu shot, according to the agency.
The COVID-19 era brings new hesitancy as critics decry politicization of the nation's premier public health agency. When the CDC changes its guidance to match Trump administration priorities, it contributes to rising distrust that may be worse than the doubts spawned by the 1976 "swine flu fiasco," says Alex Navarro, PhD, assistant director of the Center for the History of Medicine at the University of Michigan.
"What we're seeing now is the rapid deterioration of that CDC reputation as a place of science, truth, best public health practices, and public health guidelines," he says. "I think it will be lasting. I think it will be decades before we fully recover from the damage that's been done to the CDC."
Recent polls show declining confidence in the rapid release of a COVID-19 vaccine; in one poll, only 13% of respondents said they would want to get a vaccine immediately when it becomes available. (Another 16% said they would get it after a few weeks.) As with the 1976 swine flu vaccine, unexpected adverse events that seem linked to the vaccine could undermine confidence in vaccines more generally.
In 1976, as public health experts debated how to respond to the Fort Dix outbreak, epidemiologist Russell Alexander suggested making the vaccine but stockpiling it until there was evidence of virus spread beyond the Army post. As vaccination plans proceeded, he posed a question that became known in public health circles as “Alexander's question”: "What evidence, at what points in time, and about which things should prompt us to consider a change and to what new course?"
That question remains vital as decisions are made about whether to move forward with vaccine candidates, Fineberg says. The consequences will linger long into the future.
"Over time," Fineberg says, "public understanding and acceptance of all immunizations and vaccines will be strengthened or potentially diminished if we get the COVID-19 vaccine wrong."