Title:Equal Shot

Vaccines save millions of lives each year.

But they can only be truly effective if every individual has both the opportunity and the willingness to be vaccinated.

In response to the COVID-19 crisis—and in anticipation of future pandemics—Georgetown experts are engaged in an urgent conversation on how to deliver vaccines equitably around the globe. At the same time, the university is focused on a key barrier to vaccination within the United States: vaccine hesitancy stemming from historical racial inequities in the nation’s health care system.

Inoculation and Innovation

It sounds counterintuitive—putting a disease-causing substance into your body to actually prevent disease. For centuries, humans used this technique against smallpox by scratching matter from one person’s active sore into another person’s skin. In 1777, George Washington ordered the inoculation of the entire Continental Army against the smallpox virus. Approximately 40,000 soldiers were treated by the end of the year. The infection rate fell from
17% to 1%.

Early inoculation methods led to the development of vaccines against a host of deadly diseases, from tetanus to whooping cough. Vaccine pioneers like Edward Jenner, Louis Pasteur, and Jonas Salk continue to be celebrated.

Even with the extraordinary scientific advances of the last century, vaccines typically require years to develop and test. The mumps vac- cine took the shortest amount of time—just four years. A vaccine for AIDS still remains elusive.

Given past history, the introduction of effective COVID-19 vaccines in less than a year—including those employing messenger RNA, an entirely new technology—is nothing short of miraculous. “We’re in this remarkable situation where there’s been a global and U.S. effort to produce a vaccine for a new disease in an unprecedented amount of time,” says Jesse L. Goodman, M.D., MPH, director of Georgetown’s Center on Medical Product Access, Safety and Stewardship (COMPASS) and former chief scientist at the U.S. Food and Drug Administration.

But victory in the laboratory is only half the battle. In the case of a global pandemic like COVID-19, vaccines must be produced and distributed rapidly to keep ahead of the disease.

“This is not like turning all the ovens in the world into a bakery,” said Bruce Gellin, M.D., MPH, an affiliate of Georgetown’s Center for Global Health Science and Security, speaking to a class of students at the School of Foreign Service in February 2021. “It’s very different from drug manufacturing, which is a chemical process. Vaccines are a biological process. The last thing you want is to have people who’ve never done this get in the vaccine business.”

Gellin, currently president of global immunization at the Sabin Vaccine Institute, gained an insider’s perspective as head of the National Vaccine Program at the U.S. Department of Health and Human Services (HHS) during the H1N1 influenza pandemic. “When I was at HHS, I used to say this twice a week—there’s a vaccine world and a vaccination world. They’re totally different orbits.”

‘Nobody is Safe until Everyone is Safe’

Those working in the vaccination world face complex issues of equity and ethics. What is the responsibility of wealthy nations to supply vaccines to poorer countries? In cases of limited supply, who should get the first doses—those with the highest mortality rates, the greatest exposure, or some other measure?

For experts in global health, equitable distribution of vaccines is a moral as well as a public health imperative. “We should be doing this for our values and who we are as people,” said Mark Dybul, M.D. (C’85, M’92, H’08), co-director of Georgetown’s Center for Global Health Practice and Impact and former head of the President’s Emergency Plan for AIDS Relief (PEPFAR).

“And as we know clearly from the South African variant, unless we have the world vaccinated, we are not safe because these variants will constantly be coming. It’s important for solidarity, for humanitarianism, but it’s also absolutely important for our own protection and health here in the United States.”

COVID-19 hit the world during a time of growing nationalist and protectionist sentiment among nations from Great Britain to India to the United States, exacerbating the issue of “vaccine nationalism”—where countries prioritize their own vaccination needs. Many wealthier countries have entered into bilateral agreements and pre-ordered vast quantities of vaccines, monopolizing vaccine supply.

The U.S. has a vested interest in equitable vaccine distribution for economic and national security reasons as well as for public health,” says Matthew Kavanagh, Ph.D., a political scientist and assistant professor in Georgetown’s Department of International Health at the School of Nursing and Health Studies. “The global economy is still in a freefall, because the world is shut down. That doesn’t end if you get 70 or 80% of the U.S. vaccinated, but nobody else,” says Kavanagh, who is also director of the Global Health Policy & Politics Initiative at the O’Neill Institute for National and Global Health Law. There’s a study out from the International Chamber of Commerce estimating $9 trillion in negative impact of neglecting low- and middle-income countries.”

Other countries have stepped into the gap, notably China and Russia, whose vaccine safety and efficacy track records lack transparency. “We’re watching China and Russia use vaccines for diplomacy, including helping countries stand up production of their vaccines,” says Kavanagh. “Meanwhile, the U.S. has just not done so.”

Scaling Up

In the past several decades, the global health community has taken important steps to increase vaccine distribution to lower-income countries. In 2020, a coalition including the World Health Organization (WHO), Gavi, the Vaccine Alliance, and the Coalition for Epidemic Preparedness Innovations created COVID-19 Vaccines Global Access, or COVAX. Its goal is to distribute 2 billion doses of a safe and effective COVID-19 vaccine to the most vulnerable by the end of 2021.

However even with the incoming Biden administration pledging $4 billion of support, COVAX is severely underfunded. According to current estimates, doses of COVID-19 vaccines might not reach everyone around the world until 2024.

Kavanagh and many others have argued that the answer is not for wealthy countries merely to supply vaccines, but instead to share intellectual property and technology so that countries like Senegal, Malaysia, Vietnam, and others can produce their own vaccines. “I chair the UNAIDS Advisory Group, and I’m very conscious of just how parallel the experience of HIV and the experience of COVID-19 has been when it comes to global access,” he said. “In 1997 we saw this breakthrough of effective HIV treatment and it took a decade before it got to most people who needed it in the global south. Millions of folks died needlessly.

“What we’ve learned in that process is that the reality of politics and economics means you need multiple producers of these lifesaving goods,” he said. “Right now at the World Trade Organization, India, and South Africa have proposed a simple solution to patent barriers— that during the pandemic, in which we have a declared public health emergency of international concern, we waive patent restrictions on everything related to COVID-19. That’s how we scaled up AIDS drugs,” he added.

The new technology used in the manufacture of vaccines by Moderna and other companies further complicates expanding production, requiring that companies transfer technology. “It’s a long-term structural problem. You can’t just overnight build an mRNA vaccine facility in country X, Y, Z and expect it to work,” says Jesse Goodman. “But ultimately some of these technologies do offer the promise of being done on a more modular basis without complex facilities.”

The best long-term solution, in Goodman’s view, is to be proactive. “We need a global insurance system so that when outbreaks happen or emergencies of scale require a rapid response with large infusions of resources, the system is in place ahead of time—so that when we have the vaccines we have the ability to buy them, produce them, and distribute them. It is not going to be okay if the rest of the world waits until 2024 for vaccines. I’m hopeful that won’t happen. But it’s still too much of a gap and that’s not acceptable.”

The Fair Priority Model

Until the vaccine supply can be significantly ramped up, the world is faced with the reality of determining who will get vaccinated. The World Health Organization has devised a “fair allocation mechanism” in which all countries would receive vaccine supplies proportional to their population until 20% of people are covered.

“The WHO is made up of a constituency of nations, so there’s a reflex egalitarianism among them that leads them towards this equal proportions per capita standard,” said philosophy professor Henry Richardson, J.D., MPP, Ph.D., a senior scholar at Georgetown’s Kennedy Institute of Ethics. But, as Richardson explained, this model fails to take into account the varying impact of COVID-19 among countries.

“Think about distributing money. Money is something that everybody wants more of, and you can distribute any amount to anybody. In this case, what matters to people now is just getting fully vaccinated once. That refocuses the question away from how much people get to the question of when people get it,” explained Richardson.

“When we were working on the issue, we realized that the switch from ‘how much’ to ‘when’ reframes distributive justice problem. It made us think about how urgent it is that someone get vaccinated, leading us to focus on avoiding death as the first priority.”

Richardson was part of a team of ethicists, philosophers, and health care professionals convened last year by Ezekiel Emanuel, M.D., Ph.D., a bioethicist at the University of Pennsylvania who served on President Biden’s transition COVID-19 advisory board. Together they developed a vaccine distribution model meeting ethical standards.

In a September 2020 article titled “An Ethical Framework for Global Vaccine Allocation” published in Science, the team introduced the Fair Priority Model to COVAX, vaccine producers, and national governments. The team has since published two more papers ad- dressed to COVAX. Its model focuses on reducing premature death, using Standard Expected Years of Life Lost (SEYLL) as a metric. Priority is given to countries that would reduce more SEYLL per dose of vaccine.

“This matters because there are other countries where people dying from COVID-19 are much younger,” says Richardson, noting that studies from India indicate the greatest number of deaths occurred among individuals aged 50 to 64. “That was really a big part of what we were trying to address—taking into account the international disparities in life expectancy at birth.

“There are definitely signs that WHO and COVAX are paying attention to that view, and deliberating about whether they can take the differential need of countries into account, which I think they certainly should,” says Richardson.

Changing the Narrative

The United States has faced its own vaccine distribution issues, both because of limited supply and because it lacks an infrastructure for mass vaccination in adults. Despite the rocky start, most experts agree that all Americans who want to be vaccinated can receive shots by the summer.
Goodman believes that the more problematic issue in the U.S. will be what is called “vaccine hesitancy”—reluctance to be vaccinated due to historical inequities in testing and ongoing biases in treatment. “It’s a huge issue not just in the U.S., but globally,” he says.

Of particular concern in the United States is vaccination for African Americans. Although some polls show growing enthusiasm among the Black population for receiving the COVID-19 vaccine, the most recent statistics from the Kaiser Family Foundation indicate that half of Black adults still say they are not confident that the new vaccines have been adequately tested among African Americans. Compounding the issue is lack of access to vaccination sites in communities of color.

“I would say we’re in a different state with the COVID-19 vaccines compared with other vaccines,” says Deliya Wesley, Ph.D., MPH, scientific director for health equity research in the Healthcare Delivery Research Network at MedStar Health Research Institute and an assistant professor at Georgetown School of Medicine.

“The data show that it’s much more complex, given all the varied sources of information, the social climate, the political climate, the historical context. It’s something that’s come to a head, in a way that’s not applicable to other vaccines.”

Wesley conducted a highly successful program to increase participation of underrepresented populations in clinical trials, and she views many of the program’s strategies as effective in tackling vaccine hesitancy as well. “It was important to address the facts, acknowledge the history, identify influencers or trusted sources—all of those things absolutely translate,” Wesley says.

The common denominator, Wesley explains, is the ongoing societal abuse and mistreatment of the Black population in America. Research she conducted for the clinical trial study showed some participants’ hesitancy resulted from knowledge of well-known historic tragedies, such as the lack of treatment for syphilis sufferers in the Tuskegee Experiment. “But many of our younger participants hadn’t heard of Tuskegee,” Wesley says. “More than anything, for a lot of Black folks, there’s present-day reality.”

One longer-term strategy already underway is incorporating the history of systemic racism into the medical school curriculum. “The overhaul we’re starting to see is really huge. You don’t get to see sustainable change if we’re not teaching doctors to look at the system and how they interact with it,” Wesley says. “It begins and ends with the learners.

“The narrative is changing drastically, especially with events of the past 12 months,” she continues. “We’re at a tipping point, where the history cannot be ignored any more. There’s a real opportunity to start having that conversation.”

Vaccine Renaissance

The world will be learning lessons from COVID-19 for decades to come. Goodman sees one possible bright spot—what he calls a “renaissance” in public understanding and appreciation of vaccines.

“For much of the world, COVID-19 has been a palpable tragedy, and medical science and public health are clearly helping us find our way through it,” he says. “I’m really hopeful that it will be a very strong reinforcement of the ability of vaccines to save lives, and how much we depend on them—we take for granted that our kids don’t get measles and polio anymore. And so for both public health generally and with vaccines specifically, rather than the finish, this can be the start of something new.

Sarah Stewart (M’49): Leading the way to a novel vaccine

In the 1990s, scientists at Georgetown University Medical Center—led by Richard Schlegel, M.D., Ph.D., currently the Oscar B. Hunter Chair of Pathology— gained renown for their seminal contributions to
the development of a human papillomavirus (HPV) vaccine. The technology they co-invented, for which Georgetown received a number of international patents, has helped to prevent cervical cancer in millions of women.

This breakthrough would not have been possible without the pioneering work of another Georgetown pathologist, Sarah Stewart (M’49). The first woman to graduate from Georgetown Medical School, Stewart was a model of persistence. Initially unable to enroll because of her gender, despite holding a Ph.D. in microbiology and working at the National Institutes of Health (NIH), she took a job as a Georgetown instructor in order to be eligible to attend medical school classes. She enrolled full-time once the school began admitting women in 1947.

Defying the opinion of the scientific establishment, Stewart believed that viruses could cause cancer. After receiving her M.D., she carried on with her research at the NIH. She and colleague Bernice Eddy identified a virus now called the Stewart-Eddy Polyomavirus, and in 1958, they demonstrated that the virus could cause tumors in animals—definitively proving the virus-cancer link.

Stewart went on to serve as medical director of the National Cancer Institute. In 1971, she returned to Georgetown as a professor of pathology. Sadly, she herself died from cancer in 1976. The Sarah Stewart Student Lecture Series at the medical school is named in her honor, showcasing the continuing innovative research conducted by Georgetown Scientists