Warp Speed for a COVID Vaccine
Why It is Possible to Develop a COVID-9 More Quickly
A concerted effort is now underway to develop a vaccine against the virus that causes COVID-19. That virus is called SARS-CoV-2 and it is a member of a family of viruses called coronaviruses that range in the severity of the diseases they cause from mild cold symptoms to severe respiratory distress, organ failure, and death. Nearly everyone in the world wants to see the pandemic end, although a few misled people still insist that it is a hoax cooked up by people who want to benefit financially and/or politically from a vaccine.
The U.S. federal government is putting billions of dollars behind what it calls “Operation Warp Speed” to develop a vaccine more quickly than the decades it traditionally has taken to develop a new vaccine. We think that the phrase “warp speed” is unfortunate in this case because it reduces a very labor-intensive scientific process to something akin to science fiction (most people know about warp speed from the television show “Star Trek). Nevertheless, it is important to understand that there are several good reasons why a vaccine against SARS-CoV-2 could be developed more quickly than vaccines in the past.
Here are three of them:
1. Genomic sequencing is much faster than in the past: The first step in developing a vaccine is to know the genetic structure of the virus it is directed against. All human and other mammalian cells use double-stranded DNA as their genetic building blocks, but many viruses, like coronaviruses, use single-stranded RNA instead. Viral RNA enters the host human cell and commandeers its protein-making machinery, directing the human cell to make proteins that allow the virus to make many copies of itself. Like DNA, these instructions in the RNA molecule are written in a code comprised of bases strung together in a chain. By getting the sequence of those bases, a process known as genomic sequencing, scientists immediately know what some of the targets are for a potential vaccine. In the case of SARS-CoV-2, the whole genomic sequence of its RNA was completed in just three days back in January 2020. The ability to do this kind of rapid sequencing is only a few decades old and it gives scientists trying to develop a new vaccine an incredible head start.
Coronaviruses, like the one that causes COVID-19, have as their genetic molecule a single strand of RNA, which enters the host cell and captures its protein-making machinery (image: Shutterstock).
2. The structure of other coronaviruses was already known. SARS-CoV-2 is a member of the virus family called coronaviruses, which includes two other viruses that cause the very serious illnesses called MERS and SARS. Coronaviruses got their name from the protein spikes that protrude from the viral surface, resembling a crown, the Latin word for which is “corona.” The coronavirus that causes SARS emerged in 2002 and the one that causes MERS in 2012, so scientists have known a great deal about them for almost two decades. SARS-CoV-2 shares many structural similarities to those other potentially lethal coronaviruses, including the spike protein. Most of the vaccines now in development against SARS-CoV-2 target that spike protein.
The spikes on the surface of coronaviruses give the virus family its name and are a prime target for vaccines.
3. Thousands of scientists around the world are working to develop the COVID-19 vaccine. Many laboratories decided to focus attention on developing a COVID-19 vaccine almost as soon as the virus had been sequenced. Some dropped whatever else they were doing to join this effort.
What Will It Take?
Right now, there are around 300 anti-COVID-19 vaccine candidates in various stages of development and about three dozen already in human trials. Several have entered the third phase of new medication testing in which at least 30,000 people will randomly receive either a candidate vaccine or a placebo. The FDA has stated that in order for it to approve one of these vaccines, it must be 50% effective. That means, for example, if you vaccinate 100 people, only a maximum of 50% will get infected and that number must be statistically significantly lower than the number who get infected in the placebo group.
Effectiveness of only 50% may sound small. Shouldn’t we want a vaccine that is 100% effective. There are at least three good reasons to pick a level like 50%. First, it is possible the people who get the real vaccine (as opposed to placebo) and who do get infected may have less serious symptoms than people who get placebo and are infected. That is the case with the influenza vaccine. Second, what we are after in any vaccination program is to establish “herd” or “community” immunity. That’s the point at which enough people are immune to the virus that it no longer can find enough people to infect and peters out on its own. Third, it just may not be practical to find a vaccine in short enough a timeframe that has a higher rate of effectiveness.
Going back to the concept of herd or community immunity, Allison Aubrey of NPR did a little math for us. She begins by assuming we need between 60 and 70% of the population to be immune in order to establish community immunity, although some have estimated that even lower percentages may be sufficient. Then “if 20% of the U.S. population ends up getting exposed to the virus and developing an infection before we have a vaccine (as is estimated to be the level of immunity in the New York City metro area right now), then we would still need an additional 40% of the population to gain protection via a vaccine. And in order to get 40% of a population immune through vaccination — if you have a vaccine with 50% efficacy — ‘you're going to have to vaccinate 80% of the population,’ says Carlos del Rio, an infectious disease expert at Emory University.’”
COVID Vaccine Hesitancy
One would like to believe that everyone wants the vaccine in order to end this pandemic that has so changed and adversely affected our lives. But surveys have showed a range of between one third and one half of the population that say they would not be vaccinated when the vaccine becomes available. Some of the reasons for this reluctance are absurd, like believing the virus is a hoax or that Bill Gates is putting microchips in the vaccine in order to control peoples’ minds.
But in our experience the major reason some people fear the vaccine is precisely the reason we have written this commentary—they feel it is being rushed into production without adequate safety assessment. Some even go further to assert they cannot trust the government’s leaders or its agencies to be transparent about whether a vaccine against COVID-19 is in fact safe. Both of these objections are understandable, so we will address them in turn.
How do we know if a vaccine is safe? Remember that the large phase III clinical trials of any medication under development must involve something to which the active medication being tested is compared, in the case of putative COVID-19 vaccines that is a placebo, a shot containing only saltwater. They must also be doubled blinded, meaning that neither the researchers nor study participants know who has received active vaccine or placebo. Finally, they must involve large numbers of participants, in this case at least 30,000. During these trials, there are ongoing assessments of safety; that is, researchers ask participants a variety of questions and perform multiple tests to see whether any adverse side effects have occurred. They are unbiased in doing this because they don’t know who has received real vaccine and who has received placebo. Fairly uncommon safety problems can be uncovered because of the large number of subjects involved. If a serious side effect occurs in one out of 30,000 people, it would be a rate of 0.0033 percent. Of course, that doesn’t mean that such a rare event will crop up in the few months that these phase III trials will last, but a surveillance system will continue to scrutinize for rare adverse side effects even after a vaccine is ultimately approved.
There are a few other things to know about vaccine safety. It is true that there have been some serious problems that arose with vaccines after approval in the past. In 1955 due to a flaw in the manufacturing process, some people received live polio virus in a vaccine that was supposed to only contain attenuated non-infectious virus. The result was 51 cases of permanent paralysis and five deaths. This kind of tragedy has not happened in the subsequent 65 years of vaccinations and is highly unlikely to occur today.
More recently, in 1976 the swine flu vaccine was blamed for causing rare cases of a nervous system disorder called Guillain-Barre syndrome (GBS). In fact, the rate was one more case per 100,000 people who were vaccinated than occurs by chance. The 2009 H1N1 flu vaccine was at first said to cause rare cases of a sleep disorder called narcolepsy in some countries; subsequent studies failed to substantiate that claim in the U.S. and several other countries.
Despite these rare, and in some cases controversial, safety issues, most vaccine-related adverse effects show up early after receiving a vaccination, so even a relatively short-term study would be expected to detect most safety issues. A recent review of all safety-related issues that have cropped up between 1996 and 2015 in already marketed vaccines “found that vaccines were remarkably safe.”
The politics of anti-COVID-19 vaccine development are of course harder to assess. There is no question that the current administration wants a vaccine approved as soon as possible and some have claimed that it is pressuring researchers and drug companies to rush one into production without adequate testing. The head of the federal COVID-19 vaccine program, Moncef Slaoui, has said he would quit if he is pressured to act prematurely. The CEO’s of nine pharmaceutical companies involved in the race to develop a COVID-19 vaccine issued a letter stating they would not sacrifice safety in the process.
Data Safety and Monitoring Board
One of the farthest along phase III clinical trials of a vaccine—the one being developed jointly by the University of Oxford and drug company AstraZeneca—was halted in September 2020 because one woman developed an inflammation of the spinal cord, believed to be the rare disorder called transverse myelitis. At the time of this writing she was recovering and anticipating hospital discharge. The trial was later restarted in the UK but not in the US as of September 14, 2020.
The evaluation of an adverse side effect like this in a clinical trial usually falls to something called a data safety and monitoring board (DSMB). As in the case with the Oxford-AstraZeneca trial, the DSMB is composed of experts who are permitted to “break the blind” at periodic intervals or when something of concern arises, meaning they are allowed to know who has received the active vaccine and who has received placebo. For statistical reasons, this cannot be done by the actual researchers, only by a group of independent experts. At the time of this writing, the DSMB was still evaluating whether the case of probable transverse myelitis was related to the vaccine. Other vaccine experts said this hopefully temporary halt in the clinical trial is not uncommon and highlights the transparency needed in developing a SARS-CoV-2 vaccine.
There is of course no absolute guarantee that a new vaccine against SARS-CoV-2 will be 100% free of adverse side effects, including very rare serious ones. Nothing in science and medicine is ever 100%--some people who smoke cigarettes live to very old age and a rare person given an antibiotic will suffer a potentially life-threatening allergic reaction. But today there are large groups of scientists who will immediately and loudly complain if any shortcuts are taken in vaccine development, a phenomenon that has caused the administration and federal regulatory agencies to occasionally backdown on scientifically incompatible plans. There is every reason to believe that systems are in place to ensure that when the COVID-19 vaccine becomes available, it will have had as much effectiveness and safety testing as other vaccines and be safe.
Ultimately, the risk of a new vaccine must be weighed against the risk of not vaccinating. About half of all Americans have an underlying condition that puts them at risk for severe symptoms if they get infected with SARS-CoV-2. It is possible that the FDA will grant an emergency use authorization for a new COVID-19 vaccine even before it is formally approved for everyone in order to cover those at highest risk of severe complications. We probably aren’t going to see an end to the coronavirus pandemic without a vaccine. Against all of this, the risks of a vaccine seem acceptable for most people. We are reassured right now that although scientists and people involved with clinical trials are working feverishly to develop a vaccine, despite the hurry there is no evidence yet that dangerous shortcuts are being taken that would compromise vaccine safety. If things change, however, we and no doubt many others will quickly sound the alarm.