Now that Pfizer's COVID-19 vaccine has been approved for use in Great Britain and Canada, with approval in the U.S. likely to come in a few hours, we have to think about the likelihood that this and other vaccines on the way will end the pandemic.
We need to think about whether the pandemic shows the limits of our human mastery of nature. We also need to consider the history of how these vaccines have been developed by reviewing the basics of how vaccines work, the eight types of COVID vaccines that have been studied, and the accelerated development and emergency use authorization for these vaccines. Then we need to think about the possible scenarios for achieving the immunity that could slow down or end the pandemic.
THE BACONIAN CONQUEST OF INFECTIOUS DISEASES?
In his History of the Peloponnesian War, Thucydides gives a detailed account of the plague in Athens in 430-429 BC. He says that those people who recovered from the disease could not catch it again, or if they did, they would have mild symptoms, and it would not kill them. These people were the best ones to nurse the sick, or to study the disease, without fear of dying. Thucydides himself had survived an attack of the disease. So, without fully understanding it, he had observed the phenomenon of immunity and immunological memory. (I have written about the plague in Athens--and about how the Liberal Enlightenment has brought progress in overcoming infectious diseases--here, here, and here.)
Thucydides says while plagues were commonly thought to be sent by the gods, people discovered that praying to the gods was of no use against the plague, and so they stopped appealing to the gods for help. They also discovered that medical doctors could do little to help them, because the doctors did not understand the natural causes of the disease, and consequently they knew little about preventing or curing the disease.
Lucretius saw that human progress had been driven by the technological conquest of nature. He also understood that infectious diseases were probably caused by tiny "seeds" invisible to the human eye--what we today know to be bacteria or viruses.
So one might have foreseen that better understanding infectious diseases would depend on the technology of optical instruments and other techniques that would extend human vision to microscopic phenomena, and this knowledge might lead to medical technology for what Francis Bacon called the mastery of nature for the relief of the human estate. In The New Atlantis, Bacon described a society that supported scientific research institutions devoted to studying nature and inventing techniques for preventing and curing diseases, which would extend the human lifespan, perhaps even to immortality.
The critics of the Baconian project have complained that Bacon failed to recognize how this human power over nature would always limited by nature itself. So, for example, while some scientists in the middle of the 20th century predicted that humanity would soon conquer infectious diseases, newly emerging infectious diseases like COVID--arising from the unpredictable transmission of a new coronavirus from bats to humans--shows the limits of human mastery of nature. (I have written about the evolutionary history of the SARS-CoV-2 virus here, here, and here.)
Bacon understood this, however, because he observed that "Nature is conquered only by obeying her," and "all that man can do to achieve results is to bring natural bodies together and take them apart; Nature does the rest internally." The technology of vaccines illustrates this Baconian insight, because vaccines work only by stimulating the evolved natural working of the immune system in defending the body against parasitic pathogens that threaten human survival and reproduction.
VACCINE BASICS: HOW WE DEVELOP IMMUNITY
Natural selection favors the evolution of plants and animals that are naturally adapted for self-defense, and the immune system is one of the mechanisms of self-defense for animals. A properly functioning immune system must distinguish self from nonself, so that the system can recognize and target foreign substances that would injure or kill their victim. This system can fail, as in allergic reactions or autoimmune disorders, in which the immune system overreacts to a foreign body or attacks its own body.
The immune system has three features. All animals have innate immunity, which allows recognition of traits shared by broad ranges of pathogens (such as bacteria, fungi, and viruses) using a small set of receptors and a rapid response by various cells, proteins, and inflammation. Vertebrates have adaptive immunity, which allows recognition of traits specific to particular pathogens using a large number of receptors and a slower response by antibodies in body fluids and cytotoxic cells in body cells.
Although it does not receive as much attention as it deserves, there is a third dimension of the immune system--behavioral immunity, which includes behavioral strategies by which animals attempt to prevent infectious pathogens from invading their bodies. (I have written about this here.) One of those behavioral strategies is social distancing: social animals who can be infected by social contact with infected individuals can protect themselves by avoiding contact with those individuals who appear to be infected. But as social animals who naturally benefit from social interaction, social distancing creates a dilemma in which the animal must weigh the health benefits of avoiding infection against the social costs of being isolated from others. We could avoid infectious diseases if we all lived as solitary hermits. But few of us would want to live that way. That's the Darwinian evolutionary explanation for the moral debate we are now having over the COVID-19 lockdowns--the debate over whether the benefits of lockdowns outweigh the costs.
We could avoid the costs of behavioral immunity to protect ourselves against the pandemic, without incurring the costs of allowing the infections to spread, if we could achieve adaptive immunity through vaccination. To do this, we need vaccines that will simulate a coronavirus infection to provoke a natural immune response. And if enough people are vaccinated, we could become immune to the virus.
The body's adaptive immune system can learn to recognize new invading pathogens such as the coronavirus SARS-CoV-2. The virus uses its surface spike protein to lock onto receptors on the surface of human cells. Once inside the cell, the virus releases its RNA, so that it can hijack the cellular machinery for translating the viral RNA into proteins and then assembling those proteins into a new virus, which is then released from the cell. Viruses cannot reproduce themselves, which is why they must become parasites that use their host cells to reproduce more viruses.
Once the virus has been released from the human cell, the virus can be ingested by an antigen-presenting cell that displays viral peptides to activate T-helper cells. The T-helper cells then enable other other immune responses: B cells make antibodies that can block the virus from infecting cells, while also marking the virus for destruction. Cytotoxic T cells identify and destroy human cells that have been infected with the virus. Long-lived memory B and T cells that recognize the virus can patrol the body for months or years, and this constitutes immunity.
A coronavirus vaccine must simulate this process by exposing the body to an antigen (a foreign substance that induces an immune response) without causing disease. In the case of this virus, the antigenic target is the spike protein that is responsible for binding to the human cell receptor.
8 TYPES OF VACCINE
There are currently more than 180 COVID-19 vaccines at various stages of development. There are basically 8 types falling under 4 categories: virus vaccines, viral vector vaccines, protein-based vaccines, and nucleic-acid vaccines (Florian Krammer, "SARS-CoV-2 Vaccines in Development," Nature 586 [October 22, 2020]: 516-527).
Virus vaccines use the SARS-CoV-2 virus itself in either a weakened or inactivated form, so that it induces an immune response but without causing the disease. Traditionally, vaccines have all been virus vaccines--like the smallpox vaccine. In 1796, Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox virus. (Of course, he did this without understanding viruses.) Cowpox was a natural vaccine until the modern smallpox vaccine emerged in the 19th century--a live-virus preparation of vaccinia from calf lymph.
Viral-vector vaccines are those for which a virus such as measles or adenovirus has been genetically engineered to that it can produce coronavirus proteins in the body, which provoke an immune response. These viruses are weakened so that they cannot cause disease in the body. There are two types--those that can replicate within cells and those that cannot.
Protein-based vaccines are those in which coronavirus proteins are injected directly into the body. There are two types. Either fragments of proteins or protein shells mimic the coronavirus structure in such a way as to elicit an immune response, but they cannot cause disease because they lack genetic material.
Finally, nucleic-acid vaccines require injecting into the human cell either DNA or RNA with the genetic instructions for a coronavirus protein that prompts an immune response. Both the Pfizer and the Moderna vaccines are RNA vaccines.
That the Pfizer and Moderna vaccines are being approved for use is remarkable for two reasons. First, because no vaccines against coronaviruses have previously been licensed for use in humans. Second, because the whole technology of RNA vaccination is new.
Consequently, it becomes important that we have confidence that these radically new vaccines have been properly tested.
ACCELERATED DEVELOPMENT AND EMERGENCY USE AUTHORIZATION
Traditional vaccine development can take 15 years or more. So it's a big surprise that the development of the COVID-19 vaccine is occurring so quickly--with some vaccines now being approved after only 10-11 months of research. Does this show the speeding up of Baconian scientific progress, as scientists around the world cooperate and compete in developing new biomedical technologies that might quickly slow or end the pandemic? Or does it show undue haste that could be dangerous?
There are good reasons for the speed of this vaccine development. SARS-CoV-2 was first reported in China at the beginning of January. Within weeks, the genetic sequence of the virus was worked out, which allowed scientists to begin immediately looking for vaccine technologies. Typically, vaccine development starts with 2-4 years of preclinical research with mice before any clinical research with human subjects. But this kind of preclinical research had already been done with SARS-CoV and MERS-CoV coronaviruses, which could be applied to the study of SARS-CoV-2. Scientists could then move quickly to Phase I clinical trials with about 20-80 human, to Phase II with several hundred participants, and to Phase III with up to 3,000 participants. And while normally a pharmaceutical company would wait until after FDA approval to begin large-scale production of a vaccine, in this case companies started production during the Phase III trials, which was financially risky for them.
Usually, the regulatory review by the FDA takes 1-2 years. But in this case, an "emergency use authorization" application has prompted the FDA to do its review in 1-2 months. This will rightly create some concern as to whether the scrutiny of the testing has been strict enough to make us confident about the safety and efficacy of these vaccines.
FOUR SCENARIOS FOR VACCINATED IMMUNITY TO COVID-19
What kind of immunity can we expect to achieve through these COVID-19 vaccines? No one knows the answer to that question. But there are some educated guesses.
Vineet Menachery, a coronavirus researcher at the University of Texas Medical Branch in Galveston, suggests there are four possibilities: sterilizing immunity, functional immunity, waning immunity, and lost immunity (Helen Branswell, "Four Scenarios on How We Might Develop Immunity to Covid-19," STAT, August 25, 2020).
Sterilizing immunity would mean that once we have either been infected with the COVID virus or vaccinated with the COVID vaccine, we would never be infected by it again, because our immune system will have been so reliably and durably well-armed that the infection could not return.
Although this is the most desirable immunity, most scientists think it's unlikely to be achieved. Some scientists do believe, however, that some people are likely to achieve sterilizing immunity after an infection or a vaccination.
Functional immunity is a more likely possibility. This means that those people who have had either an infection or a vaccination would have immune systems that might not prevent new infections, but at least the immune defenses would be strong enough to prevent severe symptoms. And if people who are reinfected don't generate high levels of the virus, the spread of the virus might be slowed, and thus the virus might become less common and less dangerous.
Waning immunity is another possibility. People who have been infected or vaccinated could find their immunity weakening over time. Even so, new infections would be less severe than the first infection.
Some scientists foresee a mixed situation. Some people will have sterilizing immunity. But most people will have either functional or waning immunity.
Lost immunity would be the worst outcome: people who have had natural infections or vaccinations would lose all of their immunity within a short time, and so new infections would make them just as sick as they were with the first infection. No one believes this is likely. Anyone who generates some immunity to the SARS-CoV-2 virus is likely to hold that immunity at some level for a long time.
But then what about herd immunity? Can we be sure that sometime soon enough of us will have immunity so that the virus can no longer spread?
As some scientists have said, vaccines don't create herd immunity--rather, vaccinations create herd immunity, if enough people have them. And some have said that we might need to have 70% to 85% of the people vaccinated to achieve this.
There are two problems with this. The first is the adequate production and distribution of vaccines. The RNA vaccines require two doses. So to have enough for everyone in the world, we'll need about 15 billion doses delivered around the world!
The second problem is convincing people to be vaccinated, which belongs to the behavioral immune system. Some surveys have reported that a majority of Americans say they will not agree to be vaccinated. (Remarkably, Democrats are more inclined to vaccination than are Republicans!) If that's true, voluntary vaccination will not give us herd immunity.
Does that mean that we will have to institute mandatory vaccination? Could we do that without violating individual liberty? In the U.S., would that be unconstitutional?
This question will be the subject for my next post.