A Guide to Global COVID-19 Vaccine Efforts

Introduction

A year into the pandemic of the COVID-19 coronavirus disease, the global effort to develop and distribute an effective vaccine produced several safe and effective options. The accelerated development of multiple vaccines is unprecedented; the process typically takes eight to fifteen years.

However, the immunization of a critical mass of the world’s population—which is crucial for getting the pandemic under control—continues to confront 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 vaccinations globally?

More than twenty vaccines have been approved for general or emergency use in countries including China, Russia, the United Kingdom, and the United States. As of fall 2021, more than six billion doses had been administered worldwide. Several countries—including Portugal, Singapore, and the United Arab Emirates—have made significant progress in immunizing their citizens, while many others have vaccinated only small fractions of their populations.

The uneven rollout of vaccines has been felt sharply in places such as India, where the spread of new variants and relaxed restrictions led to a devastating surge in mid-2021 that impeded vaccine shipments elsewhere. In recent months, the World Health Organization (WHO) has warned that the lack of access to vaccines in Africa, where less than 5 percent of the population has been fully vaccinated, will prolong the pandemic.

To keep up progress, many countries are implementing or considering vaccination mandates. For example, Italy and Saudi Arabia mandated COVID-19 vaccinations for both government and private-sector workers; the United States did the same for its public sector and large private employers. Others have implemented mandates for health-care workers only. At the same time, childrens’ access to COVID-19 vaccines is gradually expanding: in China, children as young as three years old are eligible, and in Chile, children at least six years old. Elsewhere, including in the United States, vaccination is available to anyone twelve years and older.

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. The vaccines by U.S. pharmaceutical giant Pfizer and partnering German firm BioNTech and by U.S.-based Moderna are genetic-based. 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, such as that by the University of Oxford and British-Swedish company AstraZeneca.

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. Some experts believe that herd immunity for this coronavirus is unreachable, in part due to uneven vaccination rates.

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 dedicated several hundred million euros to COVID-19 vaccine development. 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 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 that initially aimed to have two billion vaccine doses available by the end of 2021. (As of fall 2021, it had delivered just over three hundred million doses.)

Private sector. The pharmaceutical industry has driven 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 vaccine, 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.

What are the leading COVID-19 vaccines?

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.

Scores of other COVID-19 vaccine candidates are undergoing large-scale clinical trials and around two hundred 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. 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. In August 2021, the FDA granted approval to the Pfizer-BioNTech vaccine, the first to receive a license in the United States. (Moderna is awaiting a decision on its application.)

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. The WHO similarly maintains an emergency use listing (EUL) for unlicensed vaccines and other medical products during a health crisis; more than half a dozen COVID-19 vaccines have been issued an EUL.

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. Since President Joe Biden took office, his administration has purchased over a billion additional doses, the vast majority of which are to be donated to other countries as part of his goal to get 70 percent of the world vaccinated by late 2022.

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; studies of the drug have shown faster rates of recovery from COVID-19 and lower risk of hospitalization. Additionally, dexamethasone, a common steroid, has been found to reduce the risk of death in severely ill COVID-19 patients. 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 hundreds of thousands of patients, research is ongoing to determine the treatment’s effectiveness. Doctors are also optimistic about the drug molnupiravir, which was shown in trials to reduce the risk of severe illness, because the pill can be easily administered to patients.

Can vaccines end the pandemic?

Even with a variety of vaccines with at least limited approval, there remains the tremendous challenge of making enough and distributing them to the global 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 struck deals with manufacturers early on to provide their own countries with more than enough doses, leaving lower-income countries unable to immunize but a small proportion of their citizens. China and India have large vaccine industries, which allows them to reserve some of their vaccine supplies for their own populations. 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 Foreign Policy op-ed, WHO Director General Tedros Adhanom Ghebreyesus echoed this, writing that leaving large swaths of the global population unprotected is “epidemiologically self-defeating.”

There have been signs of increasing global cooperation: at a virtual summit on the sidelines of the 2021 UN General Assembly, Biden announced an ambitious goal to vaccinate 70 percent of the world’s population by late 2022 with the help of vaccine donations and funding from wealthier nations. Additionally, dozens of countries at the World Trade Organization have backed a patent waiver for COVID-19 vaccines to scale up global production, but some countries oppose the idea, and negotiations are likely to be slow.

Meanwhile, new strains of the coronavirus, including the delta variant, have raised 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. In response, countries including the United States are offering booster shots for certain groups, though WHO and other health officials argue that initial doses for unvaccinated people should be prioritized over booster shots.

On top of these challenges are the public’s concerns about sped-up vaccines and side effects. An August 2021 poll by NPR, PBS NewsHour, and Marist College found that 19 percent of Americans surveyed do not intend to be vaccinated, though the number is considerably lower compared to when vaccines were first made available. “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.”