Claire Felter
Vaccines go through rigorous testing for safety and effectiveness before they are approved for public use, a process that typically takes years.
Introduction
A year into the pandemic of the COVID-19 coronavirus disease, the global effort to develop and distribute an effective vaccine produced several promising options. The accelerated development of multiple vaccines is unprecedented; the process typically takes eight to fifteen years.
Now, the immunization of a critical mass of the world’s population—which is crucial for getting the pandemic under control—is up against a new set of challenges, including dangerous new strains of the virus, global competition over a limited supply of doses, and public hesitation about the vaccines.
What is the status of COVID-19 vaccine distribution?
About a dozen vaccines have been approved for general or emergency use in countries including China, Russia, the United Kingdom, and the United States. As of spring 2021, more than a billion doses had been administered worldwide. Several countries—including Bahrain, Israel, the Seychelles, and the United States—have made significant progress in immunizing their citizens, while many others have either vaccinated only small fractions of their populations or are yet to start.
The lagging rollout of vaccines has been felt sharply in India, where the spread of new variants and relaxed restrictions have led to a devastating surge, and the country has limited its vaccine exports amid the crisis.
How does a vaccine work?
Traditionally, vaccines are dead or weakened virus molecules—known as antigens—that trigger defensive white blood cells in the immune system to create antibodies that bind to the virus and neutralize it.
There are four main types of conventional vaccines:
live vaccines use a weakened form of the virus to prompt the creation of antibodies;
inactivated vaccines use a dead version of the virus;
toxoid vaccines use toxins made by the virus to produce immunity to the part of the virus that causes disease; and
subunit, recombinant, polysaccharide, and conjugate vaccines use proteins or other pieces of the virus.
There are also several types of vaccines that use the virus’s genetic material—DNA or RNA—to prompt the body to create antibodies. More than a dozen of the COVID-19 vaccine candidates that have gone to clinical trials are genetic-based, including those by U.S. pharmaceutical giant Pfizer and partnering German firm BioNTech and by U.S.-based Moderna. No vaccine of this kind had ever been approved for commercial use in humans before the COVID-19 pandemic. Additionally, some COVID-19 vaccines rely on viral vectors, or modified versions of a different virus, to prompt an immune response. Several approved COVID-19 vaccines use viral vectors.
When most of a population has been vaccinated and is immune to a particular disease, even those who are not immune are considered protected because the likelihood of an outbreak is small. This is known as herd immunity. Chicken pox, measles, mumps, and polio are all examples of diseases for which the United States has achieved herd immunity due to vaccines. Scientists are divided about how much of a population must have COVID-19 antibodies to prevent new outbreaks, with estimates ranging from less than half to over 80 percent.
Who is involved in vaccine development?
Vaccines are frequently collaborative efforts across sectors of society, with private pharmaceutical firms teaming up with public health agencies or university labs. Here are snapshots of some of the major players in the COVID-19 vaccine field.
Governments. Public health agencies have played critical roles in supplying funds to develop COVID-19 vaccines. In the United States, President Donald Trump’s administration launched Operation Warp Speed, a project aimed at developing an effective vaccine and manufacturing enough doses for all three hundred million Americans. The effort, which pledged billions of dollars to companies with promising candidates, brought together several agencies within the Department of Health and Human Services—including the Centers for Disease Control and Prevention, the National Institutes of Health (NIH), and the Food and Drug Administration (FDA)—and the Department of Defense. The European Commission has also funded several candidates; at a virtual summit in May 2020 hosted by the European Union, world leaders, organizations, and banks pledged $8 billion for vaccine research. In China, the government has closely overseen efforts on its territory, with state-owned firms such as Sinopharm making up about two-fifths of the country’s vaccine industry.
International institutions. The World Health Organization (WHO) and other multilateral institutions such as the World Bank are focused on financing and manufacturing COVID-19 vaccines for global use, in particular to ensure fair allocation among all countries. Also at the forefront of multilateral efforts is the Coalition for Epidemic Preparedness Innovations (CEPI), a global alliance that was founded by Norway, India, the Bill & Melinda Gates Foundation, the UK-based Wellcome Trust, and the World Economic Forum. Gavi, the Vaccine Alliance—also founded by the Gates Foundation—is a public-private partnership focused on improving vaccine access for lower-income countries. In June 2020, the WHO, CEPI, and Gavi launched COVAX, a global initiative aiming to distribute two billion vaccine doses by the end of the following year. By February 2021, COVAX had begun its deliveries, sending doses first to West Africa.
Private sector. The pharmaceutical industry has been driving much of the push. Companies ranging from biotech start-ups to giants such as U.S.-based Johnson & Johnson shifted their research and development efforts to focus on COVID-19. Early research into a vaccine candidate typically receives government funding, such as NIH grants in the case of the United States, but the bulk of financing for clinical development generally comes from private sources. In the current pandemic, however, massive government funding for promising vaccines removed much of the risk for pharmaceutical companies.
Research institutions and nonprofits. Many of the COVID-19 vaccine candidates have involved a university or college assisting in preclinical research or clinical trials. In the case of the University of Oxford’s candidate, the research team was already working on vaccines for an unknown disease that could cause a pandemic; then, in January 2020, the group zeroed in on COVID-19. The Gates Foundation has been the leading nonprofit funding COVID-19 vaccine efforts.
Who are the leading COVID-19 vaccine developers?
Most of the vaccines approved for at least limited use have been developed by firms and research groups in China, Russia, and the United States. The first human trial in the United States began in Seattle in March 2020 with a vaccine by Moderna Inc. That vaccine was approved for emergency use in the United States, members of the European Union, and several other countries after it appeared highly effective in large-scale trials. A vaccine by Pfizer and BioNTech was also authorized by regulatory agencies in dozens of countries after similarly promising results. Johnson & Johnson’s vaccine was next to enter the U.S. market, in February 2021, but its distribution was put on hold in April in the United States and elsewhere after extremely rare reports of blood clotting. Days later, the FDA and CDC lifted the pause, expressing their confidence in the vaccine’s safety and noting that monitoring would continue. Meanwhile, Beijing has approved four of its candidates, all of which are being used by other nations. Russia has approved three vaccines; one of these is being distributed in tens of other countries.
Additionally, countries around the globe have endorsed a vaccine by the UK’s University of Oxford and British-Swedish company AstraZeneca that is cheaper and easier to store and transport than some others. Rare instances of blood clots were also linked to this vaccine, leading some countries to restrict its use to certain age groups or stop distribution entirely.
Dozens of other COVID-19 vaccine candidates are undergoing large-scale clinical trials and around 180 potential vaccines are in preclinical development by pharmaceutical companies, academic institutions, and government agencies.
How is a vaccine developed?
There are many stages involved in the development and production of a vaccine, from initial academic research to distribution to hospitals and doctor’s offices.
Clinical trials are crucial indicators of whether a vaccine is effective. Potential vaccines, as with other drugs, are commonly tested in animals first. Human trials are broken up into three phases, progressively increasing the number of volunteers. If a vaccine candidate appears to be ineffective, has harmful side effects, or is too similar to existing vaccines, it won’t move on. Trials are often carried out “blind,” by which some groups are administered the vaccine and some receive a placebo.
If a vaccine candidate is considered successful in human trials, the developers can seek approval by a national or regional regulatory agency, such as the FDA or the European Medicines Agency. In the United States, less than 10 percent of all drugs that go into clinical trials make it past this part of the process. Prior to approval, a vaccine maker can ask the FDA for an emergency use authorization (EUA), which allows the sale of unapproved medical products. Pfizer and BioNTech were granted an EUA for their vaccine in the United States on December 11, and Moderna was granted one a week later.
Additionally, while the WHO does not approve drugs, the vaccine maker can request prequalification by the WHO—a process to determine quality assurance. Many low- and middle-income countries rely on WHO prequalification [PDF] when buying medicines. Finally, the vaccine must be approved by national regulators in other countries to be distributed abroad. Following approval, the vaccine can be manufactured for broad use.
The Path to a COVID-19 Vaccine
How has development been sped up amid the pandemic?
Under normal circumstances, during which the stages of vaccine development occur sequentially, a vaccine takes eight to fifteen years on average to get from the lab into the hands of health-care providers. The fastest a vaccine had ever been developed before this pandemic was four years. Following the emergence of COVID-19, however, researchers around the globe accelerated the process by carrying out stages of development simultaneously and by looking to new vaccine technologies. “I think what we’re seeing is remarkable,” says Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. “It is a scientific tour de force.”
The U.S. Operation Warp Speed timeline hinged on overlapping stages of development; mass production started for strong candidates even while clinical trials were ongoing. Before their vaccines were approved, Moderna received $2.5 billion in a deal under Warp Speed that included the purchase of one hundred million doses, while Pfizer and BioNTech signed a $1.95 billion contract to manufacture and distribute one hundred million doses of their vaccine. (Pfizer executives said they have not accepted any U.S. federal funding for the development of their vaccine.) Shortly after President Joe Biden took office, his administration bought another hundred million doses each from these companies.
Another way researchers have quickened the process is by focusing on new vaccine approaches. RNA- and DNA-based vaccines can be developed far faster than conventional vaccines, which require months at a time of growing antigens in animal or insect cells.
How are COVID-19 treatments helping?
Dozens of treatments—which would not prevent someone from being infected with COVID-19 but could help reduce the severity and duration of illness—have been developed or repurposed. Among them is the antiviral drug remdesivir, which was developed by U.S.-based Gilead Sciences and approved by the FDA. An NIH-sponsored trial of remdesivir that involved dozens of sites in the United States, Europe, and Asia showed faster rates of recovery from the virus. Some health experts are also optimistic about the use of dexamethasone, a common steroid, which was found to reduce the risk of death in severely ill COVID-19 patients in the UK. The FDA has authorized emergency use of convalescent plasma, or blood plasma of previously infected people who have created COVID-19 antibodies. Though plasma donations have already been used in tens of thousands of patients, research is ongoing to determine the treatment’s effectiveness.
Can vaccines end the pandemic?
Even with about a dozen vaccines approved for emergency use, there remains the tremendous challenge of making enough of them for the world’s population. Though multilateral initiatives such as COVAX and individual governments are investing billions of dollars to expand production plants, current global manufacturing capabilities are far below what’s needed—only about a dozen countries have the capacity to produce COVID-19 vaccines.
This task has not only motivated countries to scale up production, but also pitted them against one another amid a limited vaccine supply. Wealthy countries including Australia, Canada, and the United States have struck deals with manufacturers to provide their countries with more than enough doses for their populations, leaving lower-income countries unable to immunize but a small proportion of their citizens in the coming months. Brazil, China, and India all have large vaccine industries, which allows them to reserve some of their vaccine supplies for their own residents.
Experts including CFR’s Thomas J. Bollyky have warned that bidding wars over vaccines lead to inequitable distribution and, ultimately, fail to eliminate the risk of new outbreaks. In a February 2021 op-ed, WHO Director General Tedros Adhanom Ghebreyesus echoed this, writing that leaving large swaths of the global population unprotected is “epidemiologically self-defeating.” However, there have been signs of increasing global cooperation: Group of Seven (G7) nations have committed billions of dollars toward equitable vaccine access, including $4 billion from the United States toward COVAX over the next two years; the UN Security Council also adopted a resolution on unhindered vaccine access in areas of armed conflict.
Meanwhile, several new strains of the coronavirus are raising concerns among scientists and health officials about increased transmission, waning immunity in people already infected with COVID-19, and reduced effectiveness of vaccines that have already been developed. Pfizer, BioNTech, and Moderna are already developing booster shots to increase protection against the new strains. Ahead of U.S. approval for its vaccine, Johnson & Johnson reported that its shot provided higher protection against these strains in clinical studies than initially thought.
On top of these challenges are the public’s concerns about sped-up vaccines and side effects. In a February 2021 poll by the Pew Research Center, 30 percent of Americans surveyed said they would not get a coronavirus vaccine. Following the Johnson & Johnson pause, the majority of unvaccinated Americans polled said they were unwilling to get that vaccine. “We’ve not done a really good job of saying, ‘Here’s what happens if you get this vaccination and here’s what happens if you don’t’,” says Georges C. Benjamin, executive director of the American Public Health Association. “We’ve not married those two stories in a compelling way for a lot of people who are fundamentally hesitant.”
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