Ralph Baric, PhD
Ralph Baric, PhD, is a professor in the department of epidemiology and professor in the department of microbiology and immunology at the University of North Carolina at Chapel Hill.
In May, the U.S. government announced Operation Warp Speed—a $20 billion program to quickly develop vaccines for the novel coronavirus (named SARS-CoV-2). The goal is to have one or more vaccines available to Americans by January 2021.
Worldwide, the pandemic has already killed hundreds of thousands of people and, without a vaccine, will likely kill millions more. This grim reality has motivated governments, scientists, and nonprofits to think and act creatively to shorten the vaccine development process. Here’s a look at what that means.
One approach is to complete many of the traditional vaccine-development steps simultaneously instead of sequentially.
The first step in vaccine development is finding an effective antigen, a compound that stimulates the production of antibodies, proteins that direct specialized T and B immune cells to block or kill the targeted virus and virus-infected cells, and to patrol the body for months or years afterward. In the case of coronavirus vaccines, multiple antigens are being tested, including the virus itself, either in a weakened or inactivated form; a coronavirus protein, usually the “spike proteins” on the surface of the virus; the genetic instructions (messenger RNA or messenger DNA) of a coronavirus protein; or a genetically engineered adenovirus that can produce coronavirus proteins without itself causing infection.
If an antigen is found, the antigen-
containing vaccine is tested in small animals, such as mice, to see if they produce antibodies and resist deadly infection. If they do, the vaccine is next tested in larger animals, usually primates.
If those tests are successful, researchers move to a phase 1 safety trial to test dosages and safety on a small number of people. If the vaccine seems safe, a phase 2 trial assesses safety in a wider group, typically hundreds of people in various age groups.
If the phase 2 trial indicates that the vaccine is safe and effective, a phase 3 efficacy trial begins. In a typical phase 3 trial, approximately 20,000 people are given the vaccine and 10,000 people are given a placebo. If far fewer people in the vaccine group than the placebo group get sick—for example, 50% fewer—the vaccine has been proved to work. If there are only minor side effects, it has been proved safe.
At that point, it’s ready for manufacturing and distribution. This typically includes the construction of a new, customized production facility to create and store the vaccine, which typically takes a few years.
Not only are scientists working on the new coronavirus vaccines combining steps, but they are also working as a worldwide team. There are 140 different vaccines being developed and tested at the same time, with researchers all over the world freely sharing their results. As of late June, 10 of those vaccines were in phase 1 trials, eight were in phase 2 trials, and two were in phase 3 trials.
In one case, researchers at the
University of Oxford had already successfully developed and animal-
tested an adenovirus-based vaccine for coronavirus in response to the SARS-CoV (2003) and MERS-CoV (2012) epidemics. Based on those findings, their vaccine for SARS-CoV-2 is already in a combined phase 2/phase 3 trial.
If that vaccine proves safe and effective, the manufacturer AstraZeneca (funded by Operation Warp Speed and the charities of the Bill and Melinda Gates Foundation) plans to deliver emergency vaccines in October. Even though the vaccine is not yet approved, it’s already in production, in facilities that can produce 2 billion doses.
We don’t know yet if any of the vaccines will be effective, and there are reasons for both hope and caution. On the hopeful side: Never-before- used medical technology, such as using messenger RNA or DNA as antigens, is showing early promise. The rapid, worldwide development of COVID-19 vaccines could herald a new and more effective way to create a vaccine. On the cautious side: Vaccines are usually tested in young, healthy animals and people with robust immune systems, rather than in older animals and people with weaker immune systems. New research from Harvard Medical School shows that 26% of studies on COVID-19 treatments—vaccines, drugs, and devices—
either excluded people older than 75 or were designed in such a way to disqualify enrollment by older adults.
A possible result is that a treatment or vaccine may work in clinical trials but not in the population most vulnerable to disability and death from COVID-19: unhealthy people in their 60s, 70s, and 80s.
It’s very likely. That’s because there has been worldwide animal research on coronavirus vaccines since the SARS-CoV epidemic in 2003, and the problems that made them unsafe in animals have been mostly identified and potential solutions have been revealed. For example, early versions of these vaccines caused the immune system to attack itself, making the symptoms of the infection worse. Newer versions don’t do that.
When a vaccine is available to Americans, the U.S. Centers for Disease Control and Prevention will issue guidelines on who should get it first, most likely people who are at a high risk of exposure and severe illness. Ideally, the first recipients should include health-care workers; people age 60 and older, with an emphasis on those living in retirement communities, assisted-care facilities, and nursing homes; workers who come in contact with many other people, such as store clerks and hairdressers; frequent travelers; and high-risk individuals with conditions that predispose them to death from the virus, such as diabetes, heart disease, lung disease, and obesity. Special attention also should be given to African-American and Latino communities, who have been disproportionately affected by COVID-19. Once the vaccine is available, it will take time to reach everyone.
In a recent survey conducted by the news organization Reuters, 25 percent of Americans said they had little or no interest in taking a coronavirus vaccine. In my view, not taking the vaccine would be a mistake. There is no reason not to: It lowers the risk of both contracting and passing along a potentially fatal disease.
Even if it doesn’t kill you, virus infection can result in a lot of physical damage. There is evidence that it can cause severe, long-term lung damage, which can affect your heart, brain, and kidneys and overall quality of life, long after the primary infection has cleared.
In the 21st century, there have been eight epidemics and pandemics, an average of one every 2½ years. Each one jumped from animals into humans. Because the interface between wildlife and humans is now very close and because global travel allows for an almost instantaneous worldwide spread of pathogens, it is highly likely that there will be many similar epidemics and pandemics in the future. Commonsense measures during an epidemic or pandemic (or even flu season) like hand-washing and wearing masks—and using a vaccine when it becomes available—are imperative.
