On January 11, a Chinese team reported online the RNA genome sequence of a novel coronavirus causing a strange new pneumonia-like disease in Wuhan, China. Within 48 hours, scientists at Moderna, a Massachusetts biotechnology company, had the entire genome synthesized. Remarkably, about 60 days later, the company, in collaboration with the Vaccine Research Center at the National Institutes of Health, began a human Phase 1 clinical trial of an RNA vaccine.
Since COVID-19 began its rapid spread across the world, scientists have worked with remarkable speed at trying to understand the virus—how it causes disease; how it spreads; why some people are asymptomatic while others die; how to develop new, or repurpose old, drugs; and how to create a safe and effective vaccine as quickly as possible. The COVID-19 story illustrates the tremendous capacity and speed of science in the 21st century, and the power of international collaboration. I am a member of the Canadian COVID-19 Vaccine Task Force, charged by the government to recommend COVID-19 vaccines that the country should purchase for its population. I am optimistic that the world will have a safe and effective vaccine by the end of this year or early 2021. However, I worry that people everywhere won’t have equal access to it.
The history of vaccinology goes back to the late 1700s when Edward Jenner developed the first vaccine, for smallpox, a turning point in the war between microbes and humans. A great triumph of modern science, vaccines rely entirely on the activation of the body’s own protective immunological mechanisms. Vaccines prevent disease, are inexpensive, are easy to deliver, and have long-lasting effects. They are also the sole medicine that benefits not only vaccinated individuals but also those around them by interrupting the pathogen’s transmission within the community.
Back in the spring, most scientists, including Anthony Fauci, the top infectious-disease expert in the U.S., predicted that a vaccine would take at least 12–18 months to deliver. That time frame was viewed as wildly optimistic, even reckless, given the more typical four to six, sometimes as many as 10 to 15, years that vaccine development typically requires. Today, most scientists working in infectious disease, including Fauci, are saying the United States will know whether there’s an effective COVID-19 vaccine by the end of the year or early 2021, and one could become available by the end of 2021. That incredible speed is not being accomplished at the expense of safety; rather, it is the result of unprecedented collaboration across borders, academia, and industry.
The ideal vaccine will do three things: protect individuals from becoming infected, prevent life-altering effects for those who do get COVID-19, and block transmission of the virus to others. The vaccine does not need to be 100 percent effective at all three to be a powerful addition to our defenses against this virus.
More than 100 vaccine candidates, including one by Moderna, are being developed around the world and about 36 have already entered human clinical trials. My optimism is not simply based on a numbers game. Nine vaccine candidates have now entered Phase 3 human trials, the final step before regulatory approval. The fact that entirely different approaches to vaccine development are all yielding promising early results is highly encouraging.
I am also hopeful because of the science behind these vaccines. The technology powering RNA vaccines, for example, was initially developed to deliver genes into the body to reprogram cells to behave like stem cells. This is the kind of science that is changing all of vaccinology, not just COVID-19 vaccine development.
In the case of SARS-CoV-2, the novel coronavirus that causes COVID-19, the protein that scientists are testing as a vaccine candidate is the result of advances in the study of protein structures. The protein in question, the spike protein, is the knobbly protrusions seen in all the illustrations of SARS-CoV-2. Because most proteins have complex three-dimensional shapes, the goal is to pick the right version of the spike protein as a vaccine so that when it is introduced into someone’s body, the immune system immediately recognizes it as foreign and starts to mount a powerful immune response directed at the spike protein. The result is that the immune system is then pre-armed and ready to immediately swing into action if a person is subsequently infected by the virus.
The science is paying off. Novavax, a Maryland-based company working on this type of vaccine, recently reported the results of its Phase 1 trial. The levels of antibodies generated were stunning, about four times higher than those in individuals who are recovering from a COVID-19 infection.
Scientists are also using different strains of another virus, adenovirus, as a vector or a missile to deliver genes that code for these same spike proteins and that also provoke an immune response. The vector has been engineered in the lab to be replication-defective; that is, the vector is able to deliver the spike gene into humans but once it’s done its job, the vector cannot replicate any further. At least three groups are testing these vectors. A University of Oxford group, in partnership with AstraZeneca, has employed an adenovirus from chimpanzees and has already entered Phase 3 trials in humans. The Beth Israel Deaconess Medical Center group, in partnership with Janssen Pharmaceutica, is using Ad26, a human adenovirus, and the Chinese-based CanSino Biologics has begun Phase 3 trials with yet another human adenovirus, Ad5.
These examples are not just beautiful science (although they are beautiful science). By harnessing the increased power of the biological sciences, researchers are developing entirely new ways of rapidly developing vaccines.
My optimism doesn’t stop with these early results, although they are key. I’m also encouraged because at least five very different approaches (I’ve walked through only three above) are being explored to make a vaccine. As we say in Canada, if you want to win, you have to take many shots on goal.
Equally important is the unprecedented global collaboration among scientists around the world, as well as the high degree of cooperation between scientists and clinicians, biopharmaceutical companies, government, philanthropic funders, and regulators. They are all working together toward the common goal of developing as quickly as possible a safe and effective vaccine against COVID-19.
I don’t know which of the vaccine candidates undergoing clinical testing in humans will ultimately be shown to be safe and effective. They might all prove effective, albeit in different age groups or in people with different preexisting conditions. But the encouraging news is that all of the vaccine candidates that have entered trials in humans so far are safe and have elicited high levels of antibodies against COVID-19. Some have also been shown to activate the cellular arm of our immune system, another crucial component of our defenses against foreign pathogens.
The public-health imperative to obtain a safe and effective vaccine as quickly as possible goes hand in hand with the mandate that the approval process be above any political considerations and solely based on data from the clinical trials. Anything else risks losing the public’s confidence in a vaccine or, in a worst-case scenario, might result in a vaccine that is less effective than those that might be approved later, or the widespread administration of a vaccine that turns out to have serious adverse side effects. That would be a public-health tragedy.
Developing a vaccine and getting proper regulatory approval are just the first two steps. The world will need billions of doses and many billions of dollars to produce and disseminate the vaccine. My main concern in this whole process is that governments will not spend enough on manufacturing the vaccine to administer it to every adult on the planet. Ensuring equitable access to a vaccine is imperative, and not just a generous gesture by wealthy nations. It’s also in their best interests. If the virus is anywhere, it’s everywhere. Nations will need to show the same willingness to cooperate as the scientists from around the world, and the same generosity of spirit demonstrated by the nearly half a million people who will have volunteered to be part of a COVID-19 vaccine trial by the time this is all over.
The United States, the wealthiest nation in the world and historically the first among nations in its generosity and leadership, has yet to contribute to the various multilateral initiatives established to purchase vaccines for the developing world. To date, 75 industrialized nations have agreed to finance vaccine purchases for 90 lower-income countries. But the U.S. is not yet one of them.
The cost of manufacturing enough doses to vaccinate every adult on the planet will be in the hundreds of billions of dollars. But compared with the trillions of dollars that governments are now spending to assist individuals who have lost their jobs and to prop up their economies, $100–200 billion is a bargain and an insurance policy that developed countries cannot afford not to buy.
If people everywhere—regardless of their gender, citizenship, ethnicity, skin color, or ability to pay—have equal and timely access to a safe and effective vaccine against COVID-19, the world will come out of this pandemic stronger than it went in. The COVID-19 pandemic has put other global challenges, including climate change and the development of accessible forms of sustainable energy, on the back burner. When this pandemic is over, we need to renew our focus on the problems that faced our planet before COVID-19. If we can eradicate COVID-19 through science and global collaboration, just imagine what else we can do.