Well before last December, the world had already faced two coronavirus outbreaks in the past 20 years. Scientists began furiously working to develop vaccines, but none were successful, and many scientists turned away from this work once the outbreaks, and funding, dissipated. Some scientists kept working on coronavirus vaccines. In 2016, scientists at the Center for Vaccine Development at Texas Children's hospital had a promising vaccine candidate and just needed some funding to start testing in humans. But investors weren't interested.
That's because vaccine development, and a great deal of medical research, is driven by markets, not public health. Coronaviruses, in general, have not been a research priority. "We have a pattern in our medical research landscape in which outbreaks lead to a surge in research investment, and if and when those outbreaks wane, as they invariably do, other priorities take their place," Jason Schwartz, professor at Yale School of Public Health who studies vaccine development told NBC.
Medical research is expensive—the National Institutes of Health alone invests over $40 billion annually in medical research—but failing to properly fund research of preventive medicine can have even costlier consequences, as we're seeing with COVID-19. The United Nations trade and development agency predicts this pandemic will cost the global economy over $1 trillion. What's more, estimates put individual vaccine development project costs at over $1 billion. Part of the reason vaccine development is so costly is because it's a long, complicated process.
This coronavirus outbreak will likely cost the global economy over $1 trillion.
Generally, vaccines go through six stages of development before they can be administered to the public. During the exploratory stage, researchers investigate possible vaccine candidates. Next comes the pre-clinical stage, when the potential vaccine is tested in cell-cultures and animals to see if it produces an immune response. Many vaccines, and drugs in general, fail to make it past this stage because they either do not produce the desired results or harm the cells or animals being tested. During the SARS outbreak, for example, animals tended to develop worse symptoms after receiving some vaccines. If a vaccine candidate does make it to the other side of the pre-clinical phase, it enters the clinical phase.
During clinical development, a vaccine is tested on humans. Three phases of clinical trials ensure the safety, proper dosages, and efficacy of the vaccine. In a Phase I trial, 20-100 people receive the vaccine so developers can confirm it's safe and figure out the appropriate dosage. This phase usually lasts several months. In a phase II trial, the vaccine is tested on a few hundred people to see if it actually works and what side effects occur. Phase II trials last up to two years. The phase III trial is the longest, lasting up to four years, and further evaluates safety, efficacy, and any adverse reactions. A few hundred to a few thousand volunteers participate in a phase III trial. According to the U.S. Food and Drug Administration (FDA), only 20-30 percent of drugs move past phase III.
Once a phase III trial is successfully completed, the vaccine goes through regulatory review and approval. If the FDA approves the vaccine, it then enters the last two stages of vaccine development, manufacturing and quality control. A vaccine may also undergo a phase IV trial at this point. A phase IV trial starts after the vaccine has been approved to further study its safety and efficacy.
It takes years to develop vaccines, but scientists are working at record speeds to create one that will end this outbreak.
The whole process to develop and approve a vaccine usually takes around a decade or more. Even though some of these standards are being relaxed to get to a new coronavirus vaccine faster, the earliest possible vaccine is probably at least a year away. The now popular National Institute of Allergy and Infectious Diseases Director, Anthony Fauci, is widely quoted predicting that the soonest we'll see a vaccine is 18 months from March 2020. Scientists and clinicians still need time to ensure a vaccine is safe and effective.
Making Coronavirus Vaccines
So far, scientists think that the new coronavirus is a good target for vaccines. It doesn't appear to change quickly and SARS and MERS vaccine development work in animals gives researchers a starting point. As of March 31, the World Health Organization listed over 50 vaccine candidates in the making. Phase I clinical trials began with two of these vaccines March 16.
One of these vaccines, made by Moderna Inc., is being tested in Seattle. The other is made by CanSino Biologics Inc. and is being tested in Wuhan. While CanSino's candidate proved to be safe in animals, Moderna's candidate was approved to skip animal trials and move directly to human testing. The Moderna vaccine uses messenger RNA (mRNA), a molecule that corresponds to a particular gene sequence and carries the information cells need to make proteins. This is new technology, and no mRNA vaccine has reached phase III clinical trials yet.
The CanSino vaccine makes use of the virus that causes the common cold. A non-replicating version of this virus carries the gene for the coronavirus spike protein into human cells. Human cells can then recognize the invading coronavirus. This same approach was used to create an Ebola vaccine that China approved in 2017.
While We Wait
As Ed Yong outlined in The Atlantic, while we wait for a vaccine, a public health-centered approach will involve a long, frustrating game of "whack-a-mole with the virus." Even if a vaccine is available 18 months from now, it will be a while before most people can receive it. Some countries have guidelines to decide how limited supplies of a future COVID-19 vaccine would be distributed. In the case of a flu pandemic, UK guidelines state that healthcare workers, social workers, and those at high medical risk should be given vaccines first.
Once a vaccine is approved, we'll see shortages before everyone who wants or needs the vaccine can receive it.
There's also the matter of equitable distribution among countries. During the H1N1 or swine flu pandemic of 2009, wealthy nations bought most of the vaccines, leaving people in developing nations at greater risk. Even after donations from manufacturers and aid from the World Health Organization and the United Nations, these countries still had far fewer vaccines.
Until those issues have been sorted out, social distancing, self-quarantine, and handwashing remain our strongest tools. How long we need to keep these measures in place, and to what extent, depends on what we learn about the virus in the coming months, how effectively we stop its spread, and whether scientists develop effective treatments.
While past coronavirus outbreaks did not convince many countries to take a proactive approach to future threats, some scientists hope that this outbreak will change research and vaccine development where others have not.