Newswise — A global race is underway to develop and mass-produce an effective vaccine to counter the new, deadly, and highly infectious coronavirus disease, COVID-19, which has brought much of the world to a standstill. Many governments have warned that daily life cannot return to normal until their populations have built up antibodies to fend off the virus. Accelerated clinical trials are already underway, but vaccine development often takes years.
Developing a successful vaccine is not enough. Many countries also face the looming challenge of producing quantities necessary to provide immunity to all their citizens, and competition is already emerging over who will have access once a vaccine is ready.
What is the status of a COVID-19 vaccine?
There are more than one hundred vaccines in preclinical development by pharmaceutical companies, academic institutions, government agencies, and others. More than seventy of these are being tracked by the World Health Organization (WHO) [PDF]. Seventeen vaccine candidates, across at least ten countries, are already undergoing clinical trials. One of these has been approved for limited use by the Chinese military. While several of these candidates are already spurring hope, experts warn that it’s too early to determine which, if any, will be successful on a large scale.
United States. Four candidates are being tested in the United States. The first human trial in the country began in Seattle in March with a vaccine developed by Moderna Inc. The trial is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). In June, Moderna started larger human trials after the vaccine appeared safe in early testing. In April, trials began for a vaccine developed by American biotech firm Inovio Pharmaceuticals and funded by the Bill & Melinda Gates Foundation and the Coalition for Epidemic Preparedness Innovations (CEPI).
China. Trials for at least six other candidates are taking place in China. The biotech firm CanSino Biologics and the medical research arm of the People’s Liberation Army started trials in March for a COVID-19 vaccine, which was approved in late June for use by military personnel. The army’s research arm is also working with other biotech firms on a second candidate. The Beijing and Wuhan Institutes of Biological Products, subsidiaries of state-run Sinopharm, are working on an inactivated virus vaccine, with late-stage trials taking place in the United Arab Emirates due to a low case count in China. Researchers at the Chinese Academy of Medical Sciences are conducting trials for two other candidates. Late-stage trials for a vaccine developed by biotech firm Sinovac are set to launch shortly in Brazil.
Australia. Three vaccines are undergoing trials in Australia. One is being developed by China-based Clover Biopharmaceuticals. The U.S.-based biotech company Novavax has started trials for another candidate in Australia, and is expected to soon expand testing to the United States and other countries. The third is a repurposed tuberculosis vaccine being tested by the Murdoch Children’s Research Institute.
United Kingdom. The University of Oxford started human trials for a candidate in late April, with $25 million in funding from the UK government. In late June, the WHO’s chief scientist said the vaccine, manufactured by AstraZeneca, was likely the world’s leading candidate. Another candidate, developed by researchers at Imperial College London, is in early trials.
Germany. U.S. pharmaceutical giant Pfizer is working together with German firm BioNTech and Chinese firm Fosun Pharma on a vaccine that began human trials in April in Germany and soon after in the United States. German firm CureVac launched early trials for another vaccine candidate in June.
Clinical trials for other candidates are taking place in Russia and South Korea.
Who is involved?
Vaccines are frequently collaborative efforts across sectors of society, with private pharmaceutical firms teaming up with public health agencies or university labs. For instance, a recently approved Ebola vaccine was ultimately developed by multinational pharmaceutical company Merck but also involved Canadian and U.S. public health agencies, a tiny Iowa-based biotech firm, U.S. Defense Department researchers, and the WHO. Here are snapshots of some of the major players in the COVID-19 race.
Governments. Public health agencies play critical roles in vaccine research, supplying funds to develop a COVID-19 vaccine. For example, the U.S. Biomedical Advanced Research and Development Authority (BARDA), an agency of the U.S. Department of Health and Human Services (HHS), pledged hundreds of millions of dollars to assist the development of vaccines by Moderna and Johnson & Johnson. And the NIH, also within HHS, has partnered with more than a dozen major pharmaceutical companies to coordinate accelerated COVID-19 vaccine research. The European Commission is also funding several candidates [PDF]; and in a virtual summit hosted by the European Union, world leaders, organizations, and banks pledged $8 billion for vaccine research. In China, the government is closely overseeing efforts on its territory, with state-owned firms 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 a COVID-19 vaccine for global use, in particular to ensure fair allocation among all countries. Also at the forefront of multilateral efforts is CEPI, a global alliance that was founded by Norway, India, the 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; it focuses on improving vaccine access for lower-income countries. By early June, Gavi raised more than $2 billion to buy approved COVID-19 vaccines for global distribution.
Private sector. The pharmaceutical industry is driving much of the push toward a vaccine. Companies ranging from biotech start-ups to giants such as Johnson & Johnson, Pfizer, and Sinopharm have rapidly shifted their research and development (R&D) efforts to focus on COVID-19. While early research into a vaccine candidate typically receives government funding, such as NIH grants in the case of the United States, the bulk of financing for clinical development generally comes from private sources.
Research institutions and nonprofits. Many of the COVID-19 vaccine candidates involve 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. In January, the group zeroed in on COVID-19, and their vaccine is now in phase-three trials with thousands of volunteers in the United Kingdom, Brazil, and South Africa. The Gates Foundation has been the leading nonprofit funding COVID-19 vaccine efforts.
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:
- livevaccines use a weakened form of the virus to prompt the creation of antibodies;
- inactivatedvaccines use a dead version of the virus;
- toxoidvaccines use toxins made by the virus to produce immunity to the part of the virus that causes disease; and
- subunit, recombinant, polysaccharide, and conjugatevaccines use proteins or other pieces of the virus.
There are also several new types of vaccines that use the virus’s genetic material—DNA or RNA—to prompt the body to create antibodies. Scientists are still investigating these types for wide use in humans.
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. Chickenpox, measles, mumps, and polio are all examples of diseases for which the United States has achieved herd immunity due to vaccines.
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 regulatory agency, such as the U.S. Food and Drug Administration (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. 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. However, with the need for billions of doses of a COVID-19 vaccine, experts warn that many more production plants will be needed to fulfill the global demand. CEPI has already raised roughly half of the $2 billion it is seeking for its coronavirus response, including building specialized production plants. BARDA has also pledged to help scale up manufacturing in the United States.
Can vaccine development be sped up?
Many experts say that the timeline of twelve to eighteen months stated by U.S. officials for a COVID-19 vaccine is extremely optimistic. Under normal circumstances, during which the stages of vaccine development occur sequentially, a vaccine on average takes eight to fifteen years to get from the lab into the hands of health-care providers. The fastest a vaccine has ever been developed is five years.
However, many around the globe are seeking to accelerate the process for COVID-19 by initiating some stages of development simultaneously and by looking to new vaccine technologies. “What’s different in this context is that you have such an enormous global effort being undertaken,” says CFR’s Thomas J. Bollyky. “Any entity working in this field broadly is pursuing a COVID-19 vaccine.”
In the United States, President Donald J. Trump’s administration launched a project known as Operation Warp Speed aimed at manufacturing enough doses of an effective vaccine for all three hundred million Americans by early 2021. The project hinges on overlapping stages of development; mass production would begin for strong candidates even while clinical trials are still ongoing.
But clinical trials are difficult to speed up because antibodies take time to develop in the body. So-called challenge trials, in which patients are purposefully exposed to a disease, are another way to cut time out of the process, but they are ethically controversial. Typically, challenge trials are only done with curable diseases, such as typhoid fever, and there is no known cure for COVID-19 yet.
Another way researchers are seeking to quicken 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. However, none has ever been approved for commercial use in humans. Seven of the COVID-19 candidates in clinical trials are RNA- or DNA-based.
How could a COVID-19 treatment help?
Dozens of treatments—which would not prevent someone from being infected with COVID-19 but could help reduce the severity and duration of illness—are being developed to mitigate the health crisis in the interim. Among the most promising treatment candidates is the antiviral drug remdesivir, which was developed by U.S.-based Gilead Sciences and already authorized for emergency use by the FDA. An NIAID 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 United Kingdom.
President Trump has promoted the use of another drug, hydroxychloroquine, as a treatment for COVID-19. The drug is typically used to treat malaria and autoimmune diseases such as arthritis. Trump said in May that he himself was taking the drug preventively, despite warnings from scientists that it is not proven to be an effective COVID-19 treatment and could lead to harmful side effects.
Can a vaccine end the coronavirus pandemic?
Public officials worldwide have stressed that the pandemic likely will not end until there is an effective vaccine. Even after a vaccine is approved, however, there remains the tremendous challenge of producing enough of it for the world’s population. An estimated one billion doses would need to be manufactured just to vaccinate workers in health care and other essential industries globally, and that is if only a single dose is required for each person.
This task has both motivated countries to prepare for large-scale production, as well as pitted them against one another amid fears of a potentially limited vaccine supply. While Brazil, China, and India all have large vaccine industries, they also have among the largest populations, and they could reserve their vaccine supplies for their own citizens before opening them up to others. Some countries are seeking to strike monopoly agreements with vaccine manufacturers to avoid domestic shortages. Brazil, the United States, and the European Union have all struck deals with AstraZeneca for hundreds of millions of doses of the University of Oxford vaccine. Experts including CFR’s Bollyky have warned that bidding wars over a vaccine will lead to inequitable distribution and, ultimately, fail to eliminate the risk of new outbreaks.
Moreover, amid these extraordinary efforts to secure a vaccine, scientists are still investigating how this new coronavirus behaves and trying to answer the many questions people have about the risk it poses and how protected they will be. This includes how effective a vaccine will be against a mutating coronavirus, though researchers point out that mutations do not necessarily mean different strains of the virus or changes in its infectiousness or lethality. Uncovering such details about the virus, they say, will only help in the development of a successful vaccine.
Nathalie Bussemaker contributed to this report.