Coronavirus Vaccine Ethics

Note: as the development, testing, and distribution of vaccines for COVID-19 are ongoing at a rapid pace, the information in this document will be updated as circumstances warrant.

Vaccines pose particular ethical questions that other pharmaceuticals do not. Vaccines are given to an otherwise healthy person in hopes of preventing infection and curbing community spread of a disease. There is both a personal component and a public health component in considering the risks and benefits of taking a vaccine. Furthermore, a vaccine for COVID-19 will have its own set of ethical issues. Multiple vaccine candidates are being developed at an accelerated pace with the goal of slowing down the worldwide pandemic of COVID-19, the disease caused by SARS-CoV-2, a novel coronavirus.[1] Because of the rapid onset of the pandemic, COVID-19 is considered a global disaster. This means bioethicists must make decisions that weigh the immediacy of the effects of the disaster with ethical best practices.

Major ethical issues concerning COVID-19 vaccines include:

Are fast-tracked vaccines that short-cut Phase 3 trials, as in the case of two vaccines out of Russia and three out of China, safe?

On July 25, the Chinese Military authorized limited distribution of a COVID-19 vaccine developed by CanSinoBio following Phase 2 trials.[2] On August 11, Russia announced that its health regulator approved a COVID-19 vaccine developed by Gamaleya Research Institute for limited use in Phase 3 trials (Russia later backtracked on how widely it would distribute the vaccine).[3] Both countries likely made these announcements for political reasons, as evidenced by Russia re-naming the vaccine program Sputnik V and China’s efforts to rectify its global reputation, such as a media campaign to re-write the narrative of the origins of the coronavirus as well as efforts in “healthcare diplomacy”.[4] Additionally, the U.S. Department of Justice has indicated that both of these countries have hacked into U.S. research institutions to obtain intellectual property related to COVID-19 therapies.[5]

Most bioethicists agree that Russia’s and China’s decisions to distribute vaccines before completing Phase 3 trials are ethically problematic and potentially dangerous.[6] The vaccines could turn out to be marginally effective or not effective at all, which happens often in Phase 3 trials of vaccines. Or a vaccine could turn out to have an unforeseen side effect that was not discovered in Phase 1 or 2 trials.

Typically the drug review process begins with pre-clinical studies in the laboratory and in animal models. Once approved for clinical research in human volunteers, the drug then moves to Phase 1 studies. Phase 1 studies involve a small number of volunteers to test for side effects, minimum effective dosage, and method of administration (e.g., intravenously, orally, etc.). In Phase 1, researchers are not testing for efficacy—whether the drug works. Then the drug moves to Phase 2 trials, which involve a larger set of volunteers. This phase looks for side effects that did not show up in Phase 1, and researchers look for preliminary evidence for efficacy. Many times Phases 1 and 2 can be combined, as was the case with most of the COVID-19 vaccine candidates.[7] Finally, Phase 3 involves a large number of participants, usually around 10,000 for vaccines, and tests for efficacy as well as any long-term side effects. This process generally takes many years, and only 25–30% of drugs pass Phase 3 trials.[8]

While it varies from country to country, the coronavirus death rate is under 1% for the general population, but much higher for the elderly and vulnerable.[9] While it is troubling that over a million people worldwide have died from COVID-19, the death rate does not merit extreme and potentially unsafe measures to fast-track a vaccine. Even in the face of how quickly the SARS-CoV-2 virus can spread through a population, adverse events from the vaccine or even an ineffective vaccine would be worse. If only healthy people are given a vaccine that turns out to be ineffective and they engage in behavior that induces spread, then the ones most likely to be harmed by the faulty vaccine are the vulnerable.

Furthermore, death rates have fallen since the beginning of the pandemic, largely because medical professionals and researchers have learned how to treat the disease and how to mitigate the severe cases.[10] This buys additional time for vaccine researchers and governmental institutions to take precautions to ensure that the vaccine works and is safe. Overall, the risks to distributing a vaccine for COVID-19 before determining efficacy and safety in a large cohort (i.e., Phase 3 trials) outweigh the benefits.

Is Emergency Use Authorization by the U.S. FDA of any of the vaccine candidates valid?

While circumventing Phase 3 trials is ethically problematic, there are some things drug companies, researchers, and regulators can do to speed up Phase 3 trials. In Phase 3 trials, the investigator gives a group of volunteers either the vaccine or a placebo. Neither the investigator nor the clinical trial participant knows whether the participant received the vaccine or placebo. This ensures that the investigator or those involved in the trial do not give the participant subtle clues that he or she received the vaccine or placebo. This is called a double-blind clinical trial. Double-blind, placebo-controlled trials are the best way to determine if a drug really does perform better than a placebo.

During the trial, the drug company will do an interim analysis after a certain number of volunteers in the trial contract the disease. For example, Moderna did an interim analysis at 53 and 106 positive COVID-19 cases. To truncate the time from injection to the interim infection numbers, Moderna enrolled 30,000 people in its Phase 3 study. Typical vaccine studies enroll less than 10,000 people and take several years before infection goals are met.[11] Paradoxically, surges in COVID-19 cases could actually speed up Phase 3 trials, while lags in the number of cases would delay the trial until enough people become infected.

There are both advantages and disadvantages to this and similar protocols. On the one hand, by having a large number of people enrolled in a Phase 3 trial, rare side effects are more likely to show up and can be recorded. On the other hand, by speeding up the process, the vaccine companies will not have data on long-term safety before Emergency Use Authorization is given. Additionally, because the pool of volunteers is much larger, this exposes more people to an unproven vaccine.

Relatedly, some have questioned how long drug companies should study these vaccines before determining that they likely will not have side effects. The FDA has said that it will require at least two months of observation after half of the trial participants have received their final dose of the vaccine before granting Emergency Use Authorization. Peter Marks, director of FDA’s vaccine division, told The Atlantic that they chose two months because most adverse events show up by then.[12]

Others question whether vaccines should even be authorized under the Emergency Use Authorization designation. In a commentary article for STAT News, members of the Vaccine Working Group, an independent non-profit organization that addresses policies regarding the testing and distribution of vaccines for COVID-19, encouraged the FDA to grant early use of COVID-19 vaccines through expanded access (also called “compassionate use”) rather than Emergency Use Authorization.[13] The authors point out that the pandemic is a crisis, not an emergency, and fast-tracking the widespread distribution of vaccines was never the intention of the Emergency Use Authorization designation. Emergency Use Authorization was originally intended for bioterrorism. Expanded access has been used for meningococcal disease and yellow fever vaccines, and it would allow the most vulnerable to receive the vaccine before widespread distribution of the vaccine but would still have rigorous monitoring for safety and efficacy among the study groups. Expanded use has greater ethical oversight and requires additional informed consent requirements compared to Emergency Use Authorization.[14]

Furthermore, several members of the FDA’s Vaccines and Related Biological Products Advisory Committee are concerned that granting Emergency Use Authorization would stymie long-term assessments of safety and efficacy, which could result in the vaccine maker not acquiring enough data for a full license to sell and distribute the vaccine.[15] The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) voiced similar concerns over the lack of long-term data.[16] The FDA questioned whether the vaccine company should “un-blind” the study, allowing the volunteers who received a placebo the option of getting the vaccine, which would be permissible under Emergency Use Authorization. In doing this, researchers will no longer have a control group to compare the vaccine to. This may leave certain questions unanswered, such as whether the vaccine reduces the number of severe COVID-19 cases, or whether the vaccine prevents the spread of COVID-19. Currently, the leading vaccine candidates—Pfizer, Moderna, and AstraZeneca’s vaccines—have shown that they prevent symptomatic COVID-19 disease. It would take many more months to determine if any of these vaccines prevent spreading the disease, an important question for ascertaining which vaccine is the best vaccine for certain populations.

Overall, there are good reasons to approve giving vulnerable populations and high-risk individuals vaccines that have met their primary endpoints and shown no evidence of adverse effects after two months. However, there are also good reasons to continue studying these vaccines to ensure there is adequate data to optimize protocols on dosage and distribution in the future. In that vein, several experts argue that expanded use should be granted to COVID-19 vaccines rather than Emergency Use Authorization. Others suggest granting Emergency Use Authorization, but not “un-blinding” study participants.

Are challenge trials ethical, as in the case of the Imperial College of London in the UK?

A challenge trial is when healthy participants are given a vaccine candidate and then intentionally infected with the pathogen it is meant to protect against under controlled conditions. The Imperial College of London is leading a challenge trial to test a vaccine for COVID-19. A challenge trial for a COVID-19 vaccine presents an ethically contentious study protocol because it is intentionally infecting an individual with a novel virus whose effects, particularly long-term effects, are still not fully known.

Some question whether human challenge trials are actually that helpful. For one, this type of trial limits the demographics that can be studied. Children and the elderly, for example, are ineligible for a challenge trial, even though the elderly would be one of the populations that would most benefit from a vaccine. Also, unlike double-blind placebo-controlled trials, human challenge trials do not test whether the vaccine works when participants are engaging in normal behavior and in typical settings. The virus is administered in safe doses via a spray in the nose or mouth and according to the Imperial College London protocol, the participant will remain in a “high-level isolation unit” for observation and to prevent community spread.[17]

According to Lambkin-Williams and DeVincenzo, who have done challenge trials for a vaccine for RSV (Respiratory Syncytial Virus), these trials can be helpful in moving a drug out of Phases 1 and 2. However, they caution that because COVID-19 does not have an effective treatment, the virus used to infect trial participants should probably be a synthetic virus.[18] This would further remove the challenge trial from a realistic scenario.

The Imperial College London trial will first determine the smallest amount of SARS-CoV-2 needed to infect a patient, and then will test whether the vaccine prevents onset of COVID-19 disease in a set of young, healthy volunteers who have not had SARS-CoV-2. An article in The Lancet says that the lead researcher for the trial has conducted challenge trials for respiratory viruses for over 10 years and will do as much as he can to mitigate the participants’ risks. Even given these assurances, many people are concerned about participant safety and the public health ramifications if a participant should die from COVID-19.[19]

In general, a challenge trial for a novel virus seems to pose more risks than benefits at this time, particularly since several vaccine candidates are already in Phase 3 trials.

Is there a fair way to distribute limited doses of the vaccine, and who should receive it first?

Once a vaccine is approved by the FDA for Emergency Use Authorization, the CDC must decide on how the vaccine will be distributed. The CDC’s Advisory Committee on Immunization Practices (ACIP) had an emergency meeting on December 1, 2020 to finalize their recommendations for Phase 1a distribution of a COVID-19 vaccine. Prior to the December meeting, in November, the committee discussed whether the vaccine should be distributed after FDA approval (as opposed to conducting more long-term studies) and who should get the vaccine first.

The National Academies of Science and the CDC agree that healthcare workers should receive the vaccine first.[20] In disaster scenarios, there is a large influx of people needing medical care at once, resulting in shortages of medical professionals, supplies, and facilities. In these scenarios, the typical bioethics protocol changes from helping the most serious cases to mitigating harms. For example, in a normal emergency room setting the more severe patients are handled first followed by the ones that can wait. In a disaster setting, the patients that are easiest to treat are treated first in hopes of getting more people to assist medics with the severe cases.[21] In the case of the SARS-CoV-2 pandemic, healthcare workers are necessarily at risk of being exposed to the virus, but these healthcare workers are needed to treat severe cases. Even though healthcare workers are likely not in the most vulnerable groups (over 65 with co-morbidities), they should receive the vaccine first so there is not a shortage of medical workers. This will result in fewer deaths overall, particularly now that we know more about treating COVID-19. Additionally, one of the ACIP presenters recommended that healthcare workers in the same facility stagger vaccine distribution in case the vaccine’s side effects (fatigue and mild fever) require the healthcare worker to stay home.[22]

The CDC conducted numerical studies to see how many lives would be saved by giving the vaccine to certain populations after healthcare workers receive the vaccine. Their numbers were based on the range of possible effectiveness of the vaccine(s). They found that giving the vaccine to older adults would avert more deaths (1–11% increase in averted deaths) while initially giving the vaccine to essential workers and others at risk of infection would avert the most infections (1–5% increase in averted infections).[23]

But there are several other factors to consider when deciding who should get the vaccine. Younger people, particularly college students, seem to account for the greatest spread, but they are also less likely to suffer from severe complications. A helpful article in the New York Times pointed out that if a vaccine was only 30% effective at blocking infection but could reduce the likelihood of infecting others by 70%, then this vaccine should be given to the group that causes the most spread rather than the most vulnerable to severe COVID-19. Another group found that the vaccine should be given to people over 65 first, unless the vaccine is at least 60% effective and can be distributed to half of the population. In this case, it should be given to people that are more likely to transmit the disease.[24]

This assumes the goals of the vaccine and public health measures are to prevent deaths and severe cases, which are measured by people in the ICU. Minimizing the number of infections or the number of non-ICU hospitalizations might change the decision metrics.

As a sub-group of vulnerable populations, several studies have shown that minorities are disproportionately represented in the ICU, particularly those in Latino and African-American populations.[25] Additionally, those living in long-term care facilities have been disproportionately affected by COVID-19, as well as prisoners and others who are institutionalized.[26] This may mean these subgroups should receive priority over other subgroups of vulnerable populations. As of their December 1 meeting, the ACIP determined that residents in long-term care facilities should be the next priority after healthcare workers.

Vaccine distribution becomes more complicated on the global scale. The U.S., UK, and Canada, for example, have pre-purchased vaccines from Moderna, Pfizer, and AstraZeneca, but poorer countries (i.e., less-resourced countries) do not have the funds to pre-purchase vaccines or the manufacturing infrastructure to produce vaccines. One initiative, COVAX, led by vaccine alliance group Gavi, which partners with the WHO, UNICEF, the World Bank, and the Bill & Melinda Gates Foundation, seeks to provide 2 billion does for low and middle-income countries by the end of 2021.[27]

But not all countries are feeling the effects of the pandemic the same way. For example, Kenya has high infections but not a very high mortality rate. One study indicated that the percentage of the population that has had COVID-19 in Kenya was similar to other countries, but the mortality rate may be lower because the population’s average age is lower.[28] Population demographics might affect prioritizing which countries receive the vaccine first. Additionally, while there is much concern regarding the immediate effects of the pandemic, many poorer countries will suffer from long-term economic effects from the pandemic, another factor that may inform how many vaccines to provide to less-resourced countries.[29]

Will the first vaccine approved by the FDA be the best vaccine, and should vulnerable populations get the first vaccine or the “best” vaccine?

Another consideration that is particularly concerning to bioethicists is whether the first vaccine that will be approved for Emergency Use Authorization will be the best vaccine. There are two issues of concern: 1) how this uncertainty will affect clinical trials for other vaccines, and 2) if the populations that would be getting the first vaccine should wait until they might be able to get a better vaccine.

Before considering these two ethical issues, we need to define what is meant by “best.” In the previous section, a successful vaccine could be one that is at least 50% effective at preventing infection, but a successful vaccine may also be defined as one that prevents spread. The best vaccine may be one that has the best balance of preventing infection and curbing spread.

An article in Science magazine summarizes presentations by the National Institutes of Health bioethics department on the ethical considerations of how the first vaccine would affect subsequent vaccine trials. The presenters pointed out that since there are multiple concurrent Phase 3 clinical trials for the COVID-19 vaccine, clinicians are concerned about the placebo-controlled studies once a vaccine candidate is found. In clinical trials for therapeutics, if a particular therapy is clearly found to be effective during the clinical trial and the control group is a placebo arm, meaning they did not receive an alternative or older treatment, then the placebo arm has a right to know that there is an effective therapy and have the option of taking it.[30]

But the current trials are for a vaccine as opposed to a therapeutic. The participants are healthy individuals who do not have a disease, although they could potentially be infected with it. If a vaccine is found to be more than 50% effective and is approved by the FDA for Emergency Use Authorization, would the placebo arm of the study have a right to know that they were in the placebo group? Should they be given the option to take the vaccine?

Even after a vaccine is approved for emergency use, researchers will continue to study participants in an effort to understand how long the vaccine lasts and whether there are any long-term side effects. Informing the placebo arm that they did not receive the vaccine and giving them the option of taking it would undermine placebo-controlled studies.

Additionally, once a vaccine is approved, this may affect Phase 3 trials of other vaccines. Rather than doing a placebo-controlled double-blind study, research may be required to conduct a non-inferiority trial.[31] This would involve giving half of the participants the vaccine being tested and giving the control arm the vaccine that was approved for emergency authorization. The goal of the clinical trial then becomes to determine whether the tested vaccine performed as well as or better than the authorized one. These trials tend to take longer and are more expensive.

The second ethical issue is related to the question of what groups should be the first to get the vaccine once it is authorized. The minimal efficacy of a vaccine for FDA approval is 50%. Perhaps the first vaccine passed by the FDA prevents COVID-19 in 50% of the people who take the vaccine. The plan is to give this vaccine first to healthcare workers and then to vulnerable populations. But what if the next vaccine is 75% effective? The very populations that would benefit most from having a more effective vaccine ended up with the less effective vaccine of the two. Because these are new pharmaceuticals, the next question would be whether it was safe to give the vulnerable population the more effective vaccine after taking the less effective vaccine. The vaccine will likely not confer life-long immunity given the SARS-CoV-2 mutation rate. It may be that by the time people will require re-vaccination, they can receive a more effective vaccine.

Update: Thus far, the two vaccines that will likely be approved for Emergency Use Authorization by the FDA are Moderna and Pfizer/BioNTech’s. Both of these vaccines have demonstrated greater than 90% efficacy in preventing infection. As far as whether these are the “best” vaccines, that will depend on the goals. These may be the best vaccines for one population, but not for another. For example, the “best” vaccine for younger people might be one that is better at preventing spread, as opposed to preventing infection. It is unclear, as of this writing, whether Moderna and Pfizer/BioNTech’s vaccines prevent person-to-person spread of COVID-19.

The CDC’s Advisory Committee on Immunization Practices (ACIP) released their recommendations for who should be vaccinated in the initial phase of COVID-19 vaccination program on December 1 following an emergency meeting.[32] The committee recommends frontline healthcare personal and residents of long-term care facilities should be the first to receive the COVID-19 vaccine. They define healthcare personnel as “paid and unpaid persons serving in health care settings who have the potential for direct and indirect exposure to patients or infectious materials.” Long-term care facility residents are people who “reside in facilities that provide a variety of services, including medical and personal care, to persons who are unable to live independently.”[33]

According to Doctor Sara Oliver’s presentation at the ACIP December 1 meeting, one sub-group to consider is female healthcare workers who are pregnant or are recently postpartum. Oliver points out that 75% of the health care workforce are women, but there is no data on mRNA vaccines in pregnant or breastfeeding women.[34]

Are people morally obligated to get a COVID-19 vaccine, especially those who have already had the virus or are low-risk for severe disease?

COVID-19 is a new disease, which means researchers are still trying to determine how long immunity lasts after a person has contracted the disease and how contagious the disease is among the population. Both of these factors are important for considering whether someone is morally obligated to get a vaccine. For example, measles is a highly contagious disease that has a relatively low death rate. But, before a measles vaccine was available and millions of children contracted measles, the low death rate still resulted in hundreds of thousands of deaths. Additionally, measles is so contagious that even when 95% of the population is immunized, as was the case in the early 2000s in the U.S., small outbreaks still occurred.[35] Because of its ability to spread rapidly throughout a community, many countries mandate measles vaccines.

Once a child has had measles, he or she will be immune to the disease. Similarly and in more recent memory, children who have had chickenpox are immune to the varicella zoster virus. Those of us who had chickenpox as a child need not get the varicella vaccine because our bodies have already produced the antibodies to keep us from contracting it again. Having had chickenpox, however, means a person is at risk of getting shingles as an older adult, so there is a vaccine available for older adults to prevent shingles. Today, most states require school children to either get the varicella vaccine or show evidence of immunity.[36]

Analogously, whether a vaccine should be mandated, or if not mandated, whether one is morally obligated to get the COVID-19 vaccine, will depend on how contagious the disease is, how deadly it is, and how long antibodies last in a previously infected person. Unfortunately, because this is a novel virus, researchers are still uncovering the answers to these questions.

Studies have gone back-and-forth as to whether the number of antibodies for COVID-19 decreases rapidly after infection or last for several months and what that means for long-term immunity[37] The number of detectable antibodies does not necessarily mean the person has the same risk of getting COVID-19 a second time as he or she did the first time. The CDC has not yet made a recommendation as to whether someone who has had COVID-19 should get a vaccine.[38] According to The Washington Post, the vaccine clinical trials did not exclude people who have already had the virus. The results from these trials may inform scientists on whether a vaccine is necessary for those who have had COVID-19.[39]

Another difficulty is no one knows how many people need to be vaccinated in order to prevent community spread, also known as reaching herd immunity. The number of people that need to be immunized depends not only on how contagious the disease is and how long antibodies last, but also how effective the vaccine is at preventing spread.

Although influenza is a different class of virus than SARS-CoV-2, both viruses cause respiratory diseases. Both viruses can be deadly but are not in the majority of cases. Likely, the moral obligation of getting a SARS-CoV-2 vaccine will be similar to that of getting the flu vaccine, particularly in the future. For now, because the disease is novel and there is understandably much panic surrounding the uncertainty of a new disease, many people feel that there is a stronger moral imperative to get a vaccine at this point in time. However, whether it is unethical to refuse a vaccine might depend on factors that we cannot measure right now as well as a particular person’s situation.

Is there a reason for conscientious objections to certain vaccines based on their development (e.g., tested in fetal cell lines)?

As of this writing, 58 vaccine candidates are undergoing clinical trials (Phases 1–3 and approved for limited use).[40] Not all of these vaccines are developed using the same methods. The broad categories of vaccines are:[41]

  • Genetic vaccines
  • Viral Vector Vaccines
  • Protein-Based Vaccines
  • Inactivated or Attenuated Coronavirus Vaccines
  • Repurposed Vaccines

Vaccine development may use human cell lines that were originally derived from an aborted fetus at some point in the past. These cell lines are perpetual cell lines, meaning once the cell lines were produced from the original fetus, they will continue to actively produce cells. The two cell lines used in some of the COVID-19 vaccine candidates are HEK 293 and PER.C6 cells. The HEK 293 cells are from a female fetus that was aborted in The Netherlands in 1972. The PER.C6 cell line is a proprietary cell line that came from a fetus that was aborted in the 1980s. Most of the vaccines, if they use a human cell line during development, use HEK 293.

(Note: The Lozier Institute has a helpful chart showing which vaccines use these fetal cell lines and at which point in the research and development process they are used. The chart does not as of this writing have some of the more recent additions to the COVID-19 vaccine pool, but can be seen here: https://lozierinstitute.org/update-covid-19-vaccine-candidates-and-abortion-derived-cell-lines/)

For the majority of the vaccines being tested, if human cell lines are used, HEK 293 cells are only used during final testing to confirm antibody production. However, several of the vaccines that use viral vectors to carry DNA into cells use fetal cell lines during the entire development process. Vector-based vaccines for COVID-19 include CanSinBio’s vaccine that was approved for limited use in China and Gamaleya Research Institute’s vaccine that was approved for limited use in Russia. AstraZeneca and Johnson & Johnson’s viral vector vaccines, which are currently in Phase 3 trials, also use human fetal cell lines at all points during development.

Messenger RNA vaccines, which include Moderna’s and BioNTech/Pfizer’s vaccines do not use cell lines during development, but they used HEK 293 cell lines to confirm antibody production. Both of these vaccines are also in Phase 3 trials. NOVAVAX, a protein-based vaccine that is also in Phase 3 trials, uses HEK 293 cells to confirm antibody production. Sinovac and Sinopharm are vaccines made from inactivated or attenuated SARS-CoV-2 virus. They are approved for limited use in China and use HEK 293 cells to confirm antibody production. Other vaccines are in pre-clinical, Phase 1, or Phase 2.

Brendon Foht at The New Atlantis has a helpful article on this topic and provides a brief outline explaining why using fetal cell lines are legal under current regulations on fetal tissue research. CBHD’s forthcoming special report on fetal tissue research will cover the legal history of fetal tissue research in more detail, but Foht’s article is a good summary.[42]

Pertinent to both the legality and the ethics of COVID-19 vaccine development is that this research does not require tissue from newly aborted fetuses. The cell lines are perpetual lines whose origins are morally problematic, but their use is temporally distant.

In the major Christian traditions (Catholic, Protestant, and Orthodox) vaccines, in general, are permissible. Among Christians and those who are pro-life, people differ on whether they consider it morally acceptable to use vaccines made from cells that originally came from an aborted fetus. The Vatican’s statement on vaccines prepared from cells derived from aborted human fetuses permits the use of these vaccines if no other alternatives exist, but it encourages vying for alternatives that come from ethical sources.[43]

One of the reasons for using a standard fetal cell line, such as HEK293, is for consistency. Many of the vaccines being tested use the cell line to confirm the vaccine’s activity. Because prior research has used these cells, they have become the standard for testing whether a vaccine works. For viral vector vaccines, the human cell lines are used to house the viral vectors. Because there is one standard cell line, the same viral vector vaccine can be produced in various parts of the world.[44]

One potential solution, proposed by Foht, is the production of several vaccines, giving people options that would include a vaccine made without the use of fetal cells lines. While having vaccine options would satisfy the personal conscience of vaccine users, it does not address what many see as an endemic problem within vaccine research—the fact that it uses cells from an illicit source.

Several scientists at the Charlotte Lozier Institute propose using fetal cell lines that were obtained from spontaneous miscarriage rather than elective abortion.[45] This would be morally similar to using tissue from a deceased donor, as opposed to tissue procured from a prisoner on death row. While the result is replacing one cell line with another, the means by which the cells were obtained separates the act of killing from therapeutic research.

In many ways, this is similar to the controversy with HeLa cells in biomedical research. The ins-and-outs of how these cells were obtained and the resulting ramifications on the Lacks family are outlined by Rebecca Skloot in her book The Immortal Life of Henrietta Lacks.[46] HeLa cells are an immortal cell line that is now the standard for many studies in biomedical research. However, these cells were obtained from a tumor in Henrietta Lacks after her death from cervical cancer. Neither she nor her family consented to the use of her cells. Researchers are loath to stop using HeLa cells because in order to compare one study to another, they need to use the same cells that prior studies had used.

There are many cases in which prior research or medical practices may not be considered ethical today but were at the time. In the case of obtaining HeLa cells, during the 1950s, informed consent standards for obtaining tissue after death were not the same as they are today. We would consider the original procurement of HeLa cells ethically problematic. The solution is not to completely undo what has been done with HeLa cells, but to first ensure that now cells are obtained with consent (e.g., the Common Rule[47]) and to seek to right the wrong by involving her family in decisions for how the cells are used and providing appropriate compensation.

Similarly, the production of the HEK 293 cell line had unethical origins, although as the scientist who first developed the cell line pointed out, at the time abortions in The Netherlands were only allowed in cases where the mother’s life was at risk, so he assumed that was the circumstance for this tissue. The circumstances surrounding PER.C6 cells are different. This cell line is owned by Crucell and was developed for the sole purpose of industrial production.[48]

We can ensure that fetal tissue from elective abortions is no longer used in research, which is what the recent policies on fetal tissue research intend to do. As far as vaccine development, we can attempt to right this by seeking out other cell lines that can serve the same purpose, whether they are ethically-derived human cell lines or animal models. This does not make people who use vaccines that were tested in fetal cell lines complicit in an immoral act any more so than benefitting from research using HeLa cells does. It does mean, though, that we can seek to do better by pressing for better methods of vaccine production.

Is a vaccine necessary?

One important question is whether a vaccine for COVID-19 is merited or necessary. Respiratory viruses tend to mutate and therefore a vaccine will likely not confer lifelong immunity. Of the common respiratory viruses, only influenza has a vaccine, and researchers must make a new vaccine every flu season to accommodate the predominant strain of influenza that season. This means we will likely never truly eradicate the SARS-CoV-2 virus, but it will hopefully become less pervasive, like the SARS-CoV virus and the MERS-CoV virus. Most viruses for which we have successful vaccines (either complete eradication or life-long immunity) are “exanthematous” viruses (i.e., skin rashes), such as the ones that cause measles, smallpox, or rubella; neurologic viruses such as the one that causes polio; and hemorrhagic viruses, such as the ones that cause yellow fever or Ebola.

If the vaccine will not confer lifelong immunity and it will not eradicate the disease, then what is the goal? According to infectious disease doctors, the goal is to mitigate the severe cases.[49] This is the same goal as the flu vaccine. The flu vaccine never confers 100% immunity. You can get the flu even if you had the vaccine, but when a large percentage of people get vaccinated for the flu and the vaccine is effective that year, the chances of a vulnerable person getting the flu is much lower.

Unlike the influenza virus, the SARS-CoV-2 virus does not seem to be seasonal. More people spending more time outdoors probably decreases the spread of the virus,[50] but warm or cold weather does not seem to destroy viral particles, given the fact that virus has spread throughout the globe in various climates. The flu, on the other hand, is seasonal, so we get annual flu shots. It is unclear how often one would need to get a COVID-19 vaccine; it may be related to virus’s mutation rate. It is also unclear how long the vaccine will confer some form of immunity since studies are still being done to clarify just how long antibodies remain in the body.

In general, a vaccine will be very helpful in mitigating severe cases as well as curbing community spread. However, a vaccine will most likely not eradicate or give complete immunity to SARS-CoV-2. This means vaccine development is good, but researchers should continue to improve standard care and therapies for COVID-19.

What are mRNA vaccines, like Moderna and Pfizer/BioNTech’s, and are they safe?

Three vaccines have seen preliminary success in Phase 3 trials. Two are mRNA vaccines: Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 (Moderna worked with the National Institute of Allergy and Infectious Diseases). The third, AstraZeneca’s adenovirus vaccine, has also seen preliminary success, although as of this writing additional studies need to be done to test its efficacy at lower dosages.[51] RNA-based vaccines are new and have never been approved for clinical use, but the way the vaccine works is similar to adenovirus and DNA-based vaccines. All of these vaccines insert genetic material into the cell to produce an immune response against a virus.[52]

By way of review, RNA is a single-strand version of DNA, except the bases designated as T’s in DNA are changed to U’s in RNA. There is also an additional oxygen in the ribose molecules in RNA that are not in DNA. This is why DNA is called “deoxyribonucleic acid” while RNA is just “ribonucleic acid.” That extra oxygen means RNA degrades more easily than DNA. To prevent degradation, RNA-based vaccines must be kept at very low temperatures.

These vaccines refer to mRNA, a certain type of RNA. To understand how mRNA vaccines work, we need to look at how the cell uses naturally-occurring RNA. All of our cells house a huge amount of DNA. Machine-like proteins “unzip” DNA and turn it into RNA. In this process, the proteins make the chemical changes necessary to change T’s to U’s and add that oxygen atom to the RNA backbone. This newly-formed RNA goes through another protein that reads the chemical bases of the RNA strand like a ticker-tape. The bases are essentially a code, or message, that tells the cell how to make a certain protein, hence the name messenger RNA.

Pfizer and Moderna are vaccines that insert synthetic mRNA into cells with a message that tells the cell how to make a piece of the spike protein that sits on the surface of SARS-CoV-2. The spike protein is how any coronavirus enters cells.[53] (Those spikes surround the surface like a crown, or in Latin corona.) A cell picks up the synthetic mRNA and reads the instructions. The cell responds, not by making the spike protein, but by making a small piece of it. The body sees the piece of the spike protein on the surface of the cell and creates antibodies that will hopefully prevent the actual virus from entering cells in the event that a person is exposed to SARS-CoV-2.[54]

Additionally, because this is RNA and not DNA, the mRNA does not enter the nucleus of the cell and therefore cannot insert itself in our DNA code. It stays outside the nucleus where the proteins are.

While the technology seems new, it is based on years of research beginning in the 1990s when scientists wanted to study mRNA to make immunotherapies. Additionally, researchers knew to go after the spike protein on SARS-CoV-2 from research on the original SARS-CoV virus during and after the pandemic in 2002. The SARS-CoV pandemic was not as widespread as SARS-CoV-2 is, but it did prompt scientists to engage in extensive research on the virus in hopes of preventing any additional outbreaks. In an interview with Dr. Ai Fen, director of the emergency department at Wuhan Central Hospital, she recalls that when she received the first lab results on her patients’ unknown flu-like illness, which would later be identified as COVID-19, the report said “SARS coronavirus.”[55] SARS-CoV and SARS-CoV-2 are distinct viruses, but similar enough that research for one has aided research for the current pandemic.

The biggest ethical concern regarding mRNA vaccines is the long-term effects. Because these vaccines are new, we do not know how they will work long-term. While there is reason to believe the long-term effects would be similar to other genetic-based vaccines, the reality is that these studies have not been done.

The second issue is distribution. Pfizer/BioNTech’s vaccine must be stored at −94°F and Moderna’s at −4°F. Once thawed, Pfizer’s vaccine will last about five days before degrading while Moderna’s vaccine will last up to one month. By way of comparison, AstraZeneca’s adenovirus vaccine, which is made in a similar way to the MMR vaccine, can be stored at 36°F to 46°F and is stable for up to six months. However, AstraZeneca has other ethical issues, mentioned previously.[56]

Overall, even though vaccine development for SARS-CoV-2 has occurred at an incredibly rapid pace, the FDA, the CDC, the National Institutes of Health, as well as the companies involved have made efforts to mitigate harms as much as possible while developing an effective vaccine as quickly as possible. Furthermore, vaccine development happened quickly partly because it builds on many years of work with mRNA therapeutics and coronavirus studies following the SARS-CoV outbreak in 2002 and the MERS-CoV outbreak in 2012.

 

References


[1] See CBHD Staff, “Coronavirus: Explanations and Ethical Issues,” The Center for Bioethics & Human Dignity, March 23, 2020, https://cbhd.org/content/coronavirus-explanations-and-ethical-issues.

[2] Carl Zimmer, Jonathan Corum, and Sui-Lee Wee, “Coronavirus Vaccine Tracker,” New York Times, November 30, 2020, https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html.

[3] Zimmer, Corum, and Wee, “Coronavirus Vaccine Tracker.”

[4] Heather Zeiger, “China: Rewriting the History of COVID-19,” Mind Matters News, March 19, 2020, https://mindmatters.ai/2020/03/china-rewriting-the-history-of-covid-19/.

[5] Heather Zeiger, “Charges Reveal Extent of China-Sponsored Hacking in the West,” Mind Matters News, July 30, 2020, https://mindmatters.ai/2020/07/charges-reveal-extent-of-china-sponsored-hacking-in-the-west/.

[6] Carl Zimmer, “‘This Is All Beyond Stupid.’ Experts Worry about Russia’s Rushed Vaccine,” New York Times, August 11, 2020, https://www.nytimes.com/2020/08/11/health/russia-covid-19-vaccine-safety.html; Jon Cohen, “Russia’s Claim of a Successful COVID-19 Vaccine Doesn’t Pass the ‘Smell Test,’ Critics Say,” Science, November 11, 2020, https://www.sciencemag.org/news/2020/11/russia-s-claim-successful-covid-19-vaccine-doesn-t-pass-smell-test-critics-say.

[7] Zimmer, Corum, and Wee, “Coronavirus Vaccine Tracker.”

[8] U.S. Food & Drug Administration, “Step 3: Clinical Research,” fda.gov, January 4, 2018, https://www.fda.gov/patients/drug-development-process/step-3-clinical-research.

[9] CDC, “CDC COVID Data Tracker,” CDC.gov, https://covid.cdc.gov/covid-data-tracker/#demographics (accessed November 11, 2020).

[10] Roni Caryn Rabin, “Death Rates Have Dropped for Seriously Ill Covid Patients,” The New York Times, October 29, 2020, https://www.nytimes.com/2020/10/29/health/Covid-survival-rates.html

[11] Sarah Zhang, “The Vaccine News That Really Matters,” The Atlantic, October 19, 2020,

https://www.theatlantic.com/health/archive/2020/10/what-successful-vaccine-trial-looks-like/616775/.

[12] Zhang, “The Vaccine News That Really Matters.”

[13] Matthew W. McCarthy, David Oshinsky, and Arthur Caplan, “Make Pre-Approval Covid-19 Vaccines Available Through Expanded Access, Not an EUA,” STAT News, November 9, 2020, https://www.statnews.com/2020/11/09/expanded-access-not-eua-for-distributing-preapproval-covid-19-vaccines/; Clint Hermes, “Covid-19 Vaccines Shouldn’t Get Emergency-Use Authorization,” MIT Technology Review, November 13, 2020, https://www.technologyreview.com/2020/11/13/1012098/covid-19-vaccines-fda-emergency-use-authorization-opinion/.

[14] U.S. Food & Drug Administration, “Expanded Access: Information for Patients,” fda.gov, May 20, 2019, https://www.fda.gov/news-events/expanded-access/expanded-access-information-patients.

[15] Helen Branswell, “FDA Shows Signs of Cold Feet over Emergency Authorization of Covid-19 Vaccines,” STAT News, October 23, 2020, https://www.statnews.com/2020/10/23/fda-shows-signs-of-cold-feet-over-emergency-authorization-of-covid-19-vaccines/.

[16] Kerry Dooley Young, “CDC Panel Takes on COVID Vaccine Rollout, Risks, and Side Effects,” Medscape, October 30, 2020, https://www.medscape.com/viewarticle/940120.

[17] Diane Gbesemete et al., “Exploring the Acceptability of Controlled Human Infection with SARSCoV2—a public consultation,” BMC Medicine 18, no. 209 (2020): https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01670-2.

[18] Rob Lambkin‐Williams and John P. DeVincenzo, “A COVID-19 Human Viral Challenge Model: Learning from Experience,” Influenza and Other Respiratory Viruses 14, no. 6 (2020): https://doi.org/10.1111/irv.12797.

[19] Tony Kirby, “COVID-19 Human Challenge Studies in the UK,” The Lancet Respiratory Medicine, October 30, 2020, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30518-X/fulltext.

[20] Alicia Ault, “COVID-19 Vaccine Should Go to HCWs First, NAS Panel Says,” Medscape, October 2, 2020, https://www.medscape.com/viewarticle/938514; Young, “CDC Panel Takes on COVID Vaccine Rollout, Risks, and Side Effects.”

[21] See Donal P. O’Mathuma, Vilius Dranseika, and Bert Gordijn, eds., Disasters: Core Concepts and Ethical Theories (Springer Open, 2018).

[22] Sara Oliver, “Clinical Consideration for Populations Included in Phase 1a,” in “ACIP Presentation Slides: December 2020 Meeting,” by Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention, December 1, 2020, https://www.cdc.gov/vaccines/acip/meetings/slides-2020-12.html (PDF available for download).

[23] “Young, “CDC Panel Takes on COVID Vaccine Rollout, Risks, and Side Effects.”

[24] Kim Tingley, “Who Should Get a Covid-19 Vaccine First?” The New York Times, November 5, 2020, https://www.nytimes.com/2020/11/05/magazine/who-gets-covid-vaccine.html.

[25] Jazmyn T. Moore, “Disparities in Incidence of COVID-19 Among Underrepresented Racial/Ethnic Groups in Counties Identified as Hotspots During June 5–18, 2020 — 22 States, February–June 2020,” Morbidity and Mortality Weekly Report 69, no. 33 (2020): 1122–26, https://www.doi.org/10.15585/mmwr.mm6933e1.

[26] The COVID Tracking Project, “The Long-Term Care COVID Tracker,” The Atlantic, https://covidtracking.com/data/longtermcare (accessed November 30, 2020).

[27] “Gavi, “COVAX,” https://www.gavi.org/covax-facility (accessed November 30, 2020); Rebecca Randall, “Christians Ready to Help COVID-19 Vaccine Go to Neediest First,” Christianity Today, November 17, 2020, https://www.christianitytoday.com/news/2020/november/christian-covid-vaccine-ethical-global-distribution.html.

[28] Bob Yirka, “Exploring the Reasons Behind Kenya’s Low COVID-19 Infection and Death Rates,” Medical Xpress, November 13, 2020, https://medicalxpress.com/news/2020-11-exploring-kenya-covid-infection-death.html.

[29] Homi Kharas “The Impact of COVID-19 on Global Extreme Poverty,” Brookings Institute, October 21, 2020, https://www.brookings.edu/blog/future-development/2020/10/21/the-impact-of-covid-19-on-global-extreme-poverty/.

[30] Jon Cohen, “First Vaccine May Stymie Hunt for Better Ones,” Science, October 23, 2020, https://science.sciencemag.org/content/370/6515/389.

[31] See Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research, “Guidance Document: Non-Inferiority Clinical Trials,” U.S. FDA, November 2016, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/non-inferiority-clinical-trials.

[32] CDC, “Advisory Committee on Immunization Practices,” CDC.gov, November 19, 2020, https://www.cdc.gov/vaccines/acip/index.html.

[33] CDC, “Advisory Committee on Immunization Practices.”

[34] Oliver, “Clinical Consideration for Populations Included in Phase 1a.”

[35] WHO, “Measles” Fact Sheet, WHO.int, December 5, 2019, https://www.who.int/news-room/fact-sheets/detail/measles.

[36] CDC, “Immunization Schedules,” CDC.gov, February 3, 2020, https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html.

[37] Rebecca J. Cox and Karl A. Brokstad, “Not Just Antibodies: B Cells and T Cells Mediate Immunity to COVID-19,” Nature Reviews Immunity 20 (2020): 581–82, https://doi.org/10.1038/s41577-020-00436-4.

[38] CDC, “Frequently Asked Questions about COVID-19 Vaccination” CDC.gov, November 24, 2020, https://www.cdc.gov/coronavirus/2019-ncov/vaccines/faq.html.

[39] Carolyn Y. Johnson and Aaron Steckelberg, “What You Need to Know about the AstraZeneca, Moderna, and Pfizer Vaccines,” The Washington Post, November 30, 2020, https://www.washingtonpost.com/health/2020/11/17/covid-vaccines-what-you-need-to-know/.

[40] Zimmer, Corum, and Wee, “Coronavirus Vaccine Tracker.”

[41] Jonathan Corum, Knvul Sheikh, and Carl Zimmer, “Different Approaches to a Coronavirus Vaccine,” New York Times, May 20, 2020, https://www.nytimes.com/interactive/2020/05/20/science/coronavirus-vaccine-development.html.

[42] Brendan Foht, “Abortion and the Coronavirus Vaccine: Why We Need an Option That Will Be Morally Acceptable to All Americans,” The New Atlantis, June 8, 2020, https://www.thenewatlantis.com/publications/abortion-and-the-coronavirus-vaccine.

[43] “Moral Reflections on Vaccines Prepared from Cells Derived from Aborted Human Foetuses,” The Linacre Quarterly 86, no. 2–3 (2019): 182–87, https://www.doi.org/10.1177/0024363919855896.

[44] Ivan Couronne, “How Fetal Cells from the 1970s Power Medical Innovation Today,” Medical Express, October 20, 2020, https://medicalxpress.com/news/2020-10-fetal-cells-1970s-power-medical.html.

[45] Charlotte Lozier Institute, “Use of Aborted Fetal Tissue: Questions & Answers,” June 5, 2019, https://lozierinstitute.org/use-of-aborted-fetal-tissue-questions-answers/, Q4(b): “Are there alternatives to use of aborted fetal tissue in research? There are many alternatives. One is use of miscarried tissue, which can be used to study development as well as causes of pregnancy loss.”

[46] Rebekah Skloot, The Immortal Life of Henrietta Lacks (New York: Broadway Paperbacks, 2011).

[47] The Common Rule is the U.S. Federal Policy for the protection of human subjects and is influenced by the Belmont Report. The Common Rule was published in 1991 and then revised in 2018 to include guidelines for research with human tissue and using genetic information. This policy informs institutional review boards on whether to approve research involving human subjects or human materials. See U.S. Department of Health & Human Services, “Federal Policy for the Protection of Human Subjects (‘Common Rule’),” HHS.gov, March 18, 2016, https://www.hhs.gov/ohrp/regulations-and-policy/regulations/common-rule/index.html.

[48] Gina Kirschweger, “Crucell: Biopharmaceuticals—As Human as They Get,” Entrepreneur 7, no. 1 (2003): 5–6, https://doi.org/10.1016/S1525-0016(02)00045-X.

[49] Sarah Zhang, “A Vaccine Reality Check,” The Atlantic, July 24, 2020, https://www.theatlantic.com/health/archive/2020/07/covid-19-vaccine-reality-check/614566/.

[50] CDC, “How COVID-19 Spreads,” CDC.gov, October 28, 2020, https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html.

[51] Reuters Staff, “AstraZeneca CEO Expects to Run New Global Trial of COVID-19 Vaccine: Bloomberg,” Reuters, November 26, 2020, https://www.reuters.com/article/us-health-coronavirus-astrazeneca/astrazeneca-ceo-expects-to-run-new-global-trial-of-covid-19-vaccine-bloomberg-idUSKBN28620H.

[52] Jennifer Abbasi, “COVID-19 and mRNA Vaccines—First Large Test for a New Approach,” JAMA 324, no. 12 (2020): 1125–27, https://doi.org/10.1001/jama.2020.16866.

[53] Abbasi, “COVID-19 and mRNA Vaccines.”

[55] Lily Kuo, “Coronavirus: Wuhan Doctor Speaks Out against Authorities,” The Guardian, March 11, 2020, https://www.theguardian.com/world/2020/mar/11/coronavirus-wuhan-doctor-ai-fen-speaks-out-against-authorities.

[56] Charlotte Lozier Institute, “Use of Aborted Fetal Tissue: Questions & Answers.”