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This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.
Even as two promising vaccine candidates for SARS-CoV-2 appear to be on the verge of emergency approval by the U.S. Food and Drug Administration, the hardest work may yet be ahead for the nation’s health care providers as they labor to instill public trust in vaccines while record-breaking levels of COVID-19 infection, hospitalization and death continue to sweep the country.
“Even the best vaccine is only as good as the number of people who get it,” said Harvard Medical School Dean George Q. Daley. “Earning the public’s trust is key, and we are facing a severe challenge: public skepticism and vaccine hesitancy.”
Despite the challenges ahead, Daley said, deployment of vaccines less than a year after the discovery of a new disease is a major triumph for biomedical science.
“Before [COVID-19], the typical timeline for vaccine development might have been three to nine years, Daley said at a Dec. 9 public briefing on COVID-19 vaccines hosted by the Harvard Medical School-led Massachusetts Consortium on Pathogen Readiness (MassCPR), which was conducted by teleconference.
To discuss the next steps needed for successful deployment of vaccines, Daley convened a panel with wide-ranging expertise on virology, vaccine development, safety regulations, vaccine deployment and the clinical treatment of COVID-19.
The presenters expressed optimism for the U.S. rollout of the first two vaccines produced by Moderna and Pfizer, however they also emphasized the need for continued public health efforts and for equitable vaccine distribution until the vaccines reach full potency in the population. They noted that continued scientific efforts to learn more about all vaccine candidates and effects, and about coronavirus, will also be crucial.
Bruce Walker, the Phillip T. and Susan M. Ragon Professor of Medicine at Massachusetts General Hospital and co-director of MassCPR, gave a brief overview of the unprecedented, rapid development of vaccines for SARS-CoV-2, noting that many have wondered how the vaccines can have been developed so quickly without compromising safety.
“The answers to that are not due to cutting corners but really to tremendous scientific advances—and to some decisions that were made early on to accelerate those aspects that could be safely accelerated,” said Walker, who is director of the Ragon Institute of MGH, MIT and Harvard. He noted that advances in genetic sequencing and unprecedented scientific collaborations hastened the speed of vaccine development.
In addition, he said, the massive scale of the clinical vaccine trials in the U.S., coupled with tragically high infection rates throughout the period of the studies, enabled rapid accumulation of data on the efficacy of the vaccines because rates of disease in the placebo arm of the studies were quite high.
For the Pfizer and Moderna vaccines, Walker said, studies showed that the vaccines were nearly 95 percent effective.
He explained that the two vaccine candidates are mRNA vaccines, which induce an immune response by delivering a snippet of the virus’s genetic code into cells in a bubble of lipid.
The mRNA vaccines use a relatively new technology, but they are not untested, Walker said, noting that several vaccines of this type have been in trials for a number of years with no serious safety concerns surfacing.
Need for transparency
Margaret Hamburg, former commissioner of the FDA, shared insights into the vaccine approval process and said the news is encouraging.
She said the U.S. is clearly on track to move forward to broader availability of first the Pfizer and then the Moderna vaccines later in December, “unless something very surprising emerges over the next few days.”
“This is happening during the darkest period of the coronavirus pandemic, in terms of what's happening in our country and many parts of the world,” Hamburg said, adding that although the good vaccine news is welcome, COVID-19 will continue to have devastating impact for months to come.
When the vaccines are deployed, she said, there will be a need for transparency about the possibility of short-term side effects, including typical vaccine reactions such as swelling at the injection site, discomfort, fatigue and headaches, so that those vaccinated are not surprised if they experience symptoms.
She emphasized the importance of preemptively discussing the fact that some potentially serious medical conditions may occur across populations following immunizations—not because vaccines cause the problems but because unrelated medical occurrences will inevitably take place during such a massive vaccination campaign. The public needs to be educated that these unrelated medical conditions are not linked to the vaccines.
In spite of these caveats, Hamburg emphasized that all available evidence suggests that the two vaccines headed for regulatory approval in the U.S. are safe. Most safety issues related to new therapies appear in the first two months of a trial, and she noted, these vaccine trials have been underway for much longer than that.
“We know most of what we can expect to see from these vaccines,” Hamburg said.
Surprisingly effective
Panelist Robert Finberg, chair of the Department of Medicine at the University of Massachusetts Medical School, along with Simone Wildes, associate director of infectious disease at South Shore Health and clinical assistant professor of medicine at Tufts Medical Center, joined Larry Madoff, the medical director in the Bureau of Infectious Disease and Laboratory Sciences at the Massachusetts Department of Public Health, in a question and answer session with forum participants.
The experts noted that the two vaccines up for approval in the U.S. have been surprisingly effective at preventing disease and reducing the risk of severe disease. They emphasized, however, that questions remain to be answered as to how long immunity will last, as well as how protection will vary across populations and age groups and among people with different comorbidities and immune profiles.
They also highlighted the challenges of vaccine acceptance, particularly among communities of color that have been especially hard hit by the virus, along with other groups that are skeptical of science because of the politicization of the pandemic.
Another challenge, they said, will be management of the complex distribution process required for such a massive, global vaccination campaign, especially with special, low-temperature storage requirements for some of the vaccines and the additional need to track administration of the second doses that are recommended for the U.S. vaccines.
Daley said health care leadership must also guard against overconfidence.
“We need to be wary of the dangers of magical thinking, of seeing vaccines as a silver bullet,” Daley said.
All of the experts emphasized the importance of many more months of continued mask wearing, infection prevention and distancing measures as the vaccines are rolled out.
They also stressed the importance of developing a longer-term vision, both to address the deep, historic social disparities that have driven the high rates of infection and mortality in Black, Latinx and Native American communities and to ensure that the U.S. and the world are better prepared for the future pandemics that are certain to follow.
Going forward, vaccine developers will continue to study participants in the coming years under formal FDA oversight to identify any emerging safety concerns and to enhance understanding of efficacy and immune duration, they said.
Hamburg explained that, in the case of the COVID-19 vaccines, emergency-use approval will adhere to the same standards of safety and efficacy as a full approval because the vaccine will be so widely distributed to people who are healthy—as opposed to other emergency approvals that might be used for medications designed to treat people who are already sick with a disease with few treatment options.
In this case, she said, the emergency-use approval is simply a legal mechanism that allows the vaccine to flow out more quickly. Following emergency approval, the FDA will continue with the more laborious process of completing a full approval.
Federal- and state-level officials have been planning who will receive the first supplies of the vaccine that become available: frontline health workers and the elderly living in congregate settings like nursing homes will be in the first cohort to receive the vaccine, followed by others deemed essential including teachers and food service workers. The general population may receive the vaccine by summer 2021.
Madoff noted that Massachusetts has an infrastructure to track distribution because it delivers millions of doses of influenza vaccine every year using similar systems. He said the state has an immunization system that records every dose of vaccine that's given by any provider in the Commonwealth, including retail pharmacy chains, primary care physicians and clinics, with every person identified and tracked by their demographics.
He said this leaves Massachusetts well-situated to carefully track distribution and make sure everyone gets the recommended second dose and that vaccines are reaching the most affected communities and are distributed ethically and equitably.
Madoff said that in the first wave, vaccinations would be directed to clinicians who treat patients with COVID-19 as well as to those involved in other aspects of patient care, such as food service, environmental and plant operations workers. He said Massachusetts will have 60,000 doses of Pfizer vaccine to deploy for health care workers as soon as the vaccine is approved.
For any vaccination campaign to work, however, the public must be willing to be vaccinated, the panelists said.
Wildes emphasized the importance of building trust in communities of color through open and honest communications and working with spokespeople who are already trusted members of those communities.
She noted that the current distrust of vaccines evident in many of these communities has deep roots in historical injustices, citing the infamous example of the Tuskegee syphilis trial.
Successful vaccine delivery, like successful care delivery, will depend on health care’s ability to address historic inequities and to develop trusting partnerships in communities of color, Wildes said.
“A successful vaccination campaign against COVID-19 will be one of the greatest scientific success stories of our time,” Daley said.
He added that it would not have been possible to get this point without a long-running commitment to medical science.
“This dizzyingly rapid virus-to-vaccine translation of basic science into a life-saving clinical treatment has been made possible by decades-long investments in the biomedical sciences—and especially to fundamental efforts to understand the molecular machinery of both microbes and humans. A triumphant vaccine is science, medicine and public health at its best,” he said.
